huntingtin

Summary

Gene Symbol: huntingtin
Description: huntingtin
Alias: IT15, LOMARS, huntingtin, huntington disease protein
Species: human
Products:     huntingtin

Top Publications

  1. Lee J, Ivanova E, Seong I, Cashorali T, Kohane I, Gusella J, et al. Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolism. PLoS Genet. 2007;3:e135 pubmed
    The Huntington's disease (HD) CAG repeat, encoding a polymorphic glutamine tract in huntingtin, is inversely correlated with cellular energy level, with alleles over approximately 37 repeats leading to the loss of striatal neurons...
  2. Wang C, Tydlacka S, Orr A, Yang S, Graham R, Hayden M, et al. Accumulation of N-terminal mutant huntingtin in mouse and monkey models implicated as a pathogenic mechanism in Huntington's disease. Hum Mol Genet. 2008;17:2738-51 pubmed publisher
    A number of mouse models expressing mutant huntingtin (htt) with an expanded polyglutamine (polyQ) domain are useful for studying the pathogenesis of Huntington's disease (HD) and identifying appropriate therapies...
  3. Caron N, Desmond C, Xia J, Truant R. Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin. Proc Natl Acad Sci U S A. 2013;110:14610-5 pubmed publisher
    Huntington disease (HD) is a neurodegenerative disorder caused by a CAG expansion within the huntingtin gene that encodes a polymorphic glutamine tract at the amino terminus of the huntingtin protein...
  4. Furukawa Y, Kaneko K, Matsumoto G, Kurosawa M, Nukina N. Cross-seeding fibrillation of Q/N-rich proteins offers new pathomechanism of polyglutamine diseases. J Neurosci. 2009;29:5153-62 pubmed publisher
    A pathological hallmark of the Huntington's disease (HD) is intracellular inclusions containing a huntingtin (Htt) protein with an elongated polyglutamine tract...
  5. Li X, Standley C, Sapp E, Valencia A, Qin Z, Kegel K, et al. Mutant huntingtin impairs vesicle formation from recycling endosomes by interfering with Rab11 activity. Mol Cell Biol. 2009;29:6106-16 pubmed publisher
    b>Huntingtin (Htt) localizes to endosomes, but its role in the endocytic pathway is not established. Recently, we found that Htt is important for the activation of Rab11, a GTPase involved in endosomal recycling...
  6. Metzger S, Rong J, Nguyen H, Cape A, Tomiuk J, Soehn A, et al. Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease. Hum Mol Genet. 2008;17:1137-46 pubmed publisher
    A polyglutamine repeat expansion of more than 36 units in a protein called huntingtin (htt) is the only known cause of Huntington's disease (HD)...
  7. Xia J, Lee D, Taylor J, Vandelft M, Truant R. Huntingtin contains a highly conserved nuclear export signal. Hum Mol Genet. 2003;12:1393-403 pubmed
    ..CAG DNA expansion results in a polyglutamine tract expansion in mutant huntingtin protein...
  8. Caviston J, Ross J, Antony S, Tokito M, Holzbaur E. Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proc Natl Acad Sci U S A. 2007;104:10045-50 pubmed
    ..b>Huntingtin (Htt) is a vesicle-associated protein found in both neuronal and nonneuronal cells that is thought to be ..
  9. Takano H, Gusella J. The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor. BMC Neurosci. 2002;3:15 pubmed
    Huntington's disease (HD) pathogenesis is due to an expanded polyglutamine tract in huntingtin, but the specificity of neuronal loss compared with other polyglutamine disorders also implies a role for the protein's unknown inherent ..

More Information

Publications133 found, 100 shown here

  1. Humbert S, Bryson E, Cordelières F, Connors N, Datta S, Finkbeiner S, et al. The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. Dev Cell. 2002;2:831-7 pubmed
    ..of the serine/threonine kinase Akt/PKB is able to inhibit neuronal death specifically induced by mutant huntingtin containing an expanded polyglutamine stretch...
  2. Chiang M, Lee Y, Huang C, Chern Y. cAMP-response element-binding protein contributes to suppression of the A2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues. J Biol Chem. 2005;280:14331-40 pubmed
    ..disease is a neurodegenerative disease resulting from a CAG (glutamine) trinucleotide expansion in exon 1 of the Huntingtin (Htt) gene...
  3. Seong I, Ivanova E, Lee J, Choo Y, Fossale E, Anderson M, et al. HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. Hum Mol Genet. 2005;14:2871-80 pubmed
    The 'expanded' HD CAG repeat that causes Huntington's disease (HD) encodes a polyglutamine tract in huntingtin, which first targets the death of medium-sized spiny striatal neurons...
  4. Li S, Cheng A, Zhou H, Lam S, Rao M, Li H, et al. Interaction of Huntington disease protein with transcriptional activator Sp1. Mol Cell Biol. 2002;22:1277-87 pubmed
    ..In HD, N-terminal fragments of huntingtin with an expanded glutamine tract are able to aggregate and accumulate in the nucleus...
  5. Khoshnan A, Ko J, Patterson P. Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity. Proc Natl Acad Sci U S A. 2002;99:1002-7 pubmed
    ..mAbs (MW1-8) that bind the epitopes polyglutamine (polyQ), polyproline (polyP), or the C terminus of exon 1 in huntingtin (htt) protein...
  6. Lee W, Yoshihara M, Littleton J. Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington's disease. Proc Natl Acad Sci U S A. 2004;101:3224-9 pubmed
    ..disease is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine tract in the huntingtin protein that results in intracellular aggregate formation and neurodegeneration...
  7. Zala D, Colin E, Rangone H, Liot G, Humbert S, Saudou F. Phosphorylation of mutant huntingtin at S421 restores anterograde and retrograde transport in neurons. Hum Mol Genet. 2008;17:3837-46 pubmed publisher
    b>Huntingtin (htt), the protein mutated in Huntington's disease, is a positive regulatory factor for vesicular transport whose function is lost in disease...
  8. Lotz G, Legleiter J, Aron R, Mitchell E, Huang S, Ng C, et al. Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oligomers in a classic ATP-dependent reaction cycle. J Biol Chem. 2010;285:38183-93 pubmed publisher
    Inclusion bodies of aggregated mutant huntingtin (htt) fragments are a neuropathological hallmark of Huntington disease (HD)...
  9. Myers R. Huntington's disease genetics. NeuroRx. 2004;1:255-62 pubmed
    ..Testing is widely available and much experience has been gained with protocols that assist the individual in making an informed choice about test options, and minimize the occurrence of adverse emotional outcomes. ..
  10. Wang C, Zhou H, McGuire J, Cerullo V, Lee B, Li S, et al. Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin. J Cell Biol. 2008;181:803-16 pubmed publisher
    Mutant huntingtin accumulates in the neuronal nuclei and processes, which suggests that its subcellular localization is critical for the pathology of Huntington's disease (HD)...
  11. Godin J, Poizat G, Hickey M, Maschat F, Humbert S. Mutant huntingtin-impaired degradation of beta-catenin causes neurotoxicity in Huntington's disease. EMBO J. 2010;29:2433-45 pubmed publisher
    ..We report here a new pathological mechanism by which mutant huntingtin specifically interferes with the degradation of beta-catenin...
  12. Yang H, Zhong X, Ballar P, Luo S, Shen Y, Rubinsztein D, et al. Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin. Exp Cell Res. 2007;313:538-50 pubmed
    ..We tested this idea by using polyglutamine (polyQ)-containing huntingtin (htt) protein as a model substrate...
  13. Gervais F, Singaraja R, Xanthoudakis S, Gutekunst C, Leavitt B, Metzler M, et al. Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi. Nat Cell Biol. 2002;4:95-105 pubmed
    In Huntington disease, polyglutamine expansion of the protein huntingtin (Htt) leads to selective neurodegenerative loss of medium spiny neurons throughout the striatum by an unknown apoptotic mechanism...
  14. Dunah A, Jeong H, Griffin A, Kim Y, Standaert D, Hersch S, et al. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science. 2002;296:2238-43 pubmed
    ..disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine tract in the huntingtin protein. Transcriptional dysregulation has been implicated in HD pathogenesis...
  15. Huang K, Yanai A, Kang R, Arstikaitis P, Singaraja R, Metzler M, et al. Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins. Neuron. 2004;44:977-86 pubmed
    ..Here, using biochemical assays, we show that huntingtin (htt) interacting protein, HIP14, is a neuronal palmitoyl transferase (PAT)...
  16. Feng Z, Jin S, Zupnick A, Hoh J, de Stanchina E, Lowe S, et al. p53 tumor suppressor protein regulates the levels of huntingtin gene expression. Oncogene. 2006;25:1-7 pubmed
    ..The accumulation of the mutant huntingtin protein with an expanded polyglutamine tract plays a central role in the pathology of human Huntington's disease...
  17. Olshina M, Angley L, Ramdzan Y, Tang J, Bailey M, Hill A, et al. Tracking mutant huntingtin aggregation kinetics in cells reveals three major populations that include an invariant oligomer pool. J Biol Chem. 2010;285:21807-16 pubmed publisher
    Huntington disease is caused by expanded polyglutamine sequences in huntingtin, which procures its aggregation into intracellular inclusion bodies (IBs)...
  18. Yu Z, Li S, Nguyen H, Li X. Huntingtin inclusions do not deplete polyglutamine-containing transcription factors in HD mice. Hum Mol Genet. 2002;11:905-14 pubmed
    ..g. hypothalamus and amygdala), double labeling showed that most CBP was not co-localized with huntingtin nuclear inclusions. Electron microscopy confirmed that CBP was diffusely distributed in the nucleus...
  19. Steffan J, Agrawal N, Pallos J, Rockabrand E, Trotman L, Slepko N, et al. SUMO modification of Huntingtin and Huntington's disease pathology. Science. 2004;304:100-4 pubmed
    Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion...
  20. Schaffar G, Breuer P, Boteva R, Behrends C, Tzvetkov N, Strippel N, et al. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol Cell. 2004;15:95-105 pubmed
    ..We show, in vitro and in cells, that monomers or small soluble oligomers of huntingtin exon1 accumulate in the nucleus and inhibit the function of TBP in a polyQ-dependent manner...
  21. Cornett J, Cao F, Wang C, Ross C, Bates G, Li S, et al. Polyglutamine expansion of huntingtin impairs its nuclear export. Nat Genet. 2005;37:198-204 pubmed
    ..The mechanism by which mutant huntingtin (htt) accumulates intranuclearly is not known; wild-type htt, a 350-kDa protein of unknown function, is normally ..
  22. Zala D, Benchoua A, Brouillet E, Perrin V, Gaillard M, Zurn A, et al. Progressive and selective striatal degeneration in primary neuronal cultures using lentiviral vector coding for a mutant huntingtin fragment. Neurobiol Dis. 2005;20:785-98 pubmed
    A lentiviral vector expressing a mutant huntingtin protein (htt171-82Q) was used to generate a chronic model of Huntington's disease (HD) in rat primary striatal cultures...
  23. Garcia M, Charvin D, Caboche J. Expanded huntingtin activates the c-Jun terminal kinase/c-Jun pathway prior to aggregate formation in striatal neurons in culture. Neuroscience. 2004;127:859-70 pubmed
    ..disease (HD) is an autosomal neurodegenerative disorder, caused by expansion of a glutamine repeat in the Huntingtin protein...
  24. Warby S, Doty C, Graham R, Shively J, Singaraja R, Hayden M. Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments. Mol Cell Neurosci. 2009;40:121-7 pubmed publisher
    b>Huntingtin is phosphorylated on serine-421 (S421) by the pro-survival signaling protein kinases Akt and SGK...
  25. Ratovitski T, Gucek M, Jiang H, Chighladze E, Waldron E, D Ambola J, et al. Mutant huntingtin N-terminal fragments of specific size mediate aggregation and toxicity in neuronal cells. J Biol Chem. 2009;284:10855-67 pubmed publisher
    b>Huntingtin proteolysis is implicated in Huntington disease pathogenesis, yet, the nature of huntingtin toxic fragments remains unclear...
  26. Benchoua A, Trioulier Y, Zala D, Gaillard M, Lefort N, Dufour N, et al. Involvement of mitochondrial complex II defects in neuronal death produced by N-terminus fragment of mutated huntingtin. Mol Biol Cell. 2006;17:1652-63 pubmed
    ..proteins in striatal neurons that were infected with lentiviral vectors coding for the N-terminus part of huntingtin (Htt) with either a pathological (Htt171-82Q) or physiological (Htt171-19Q) polyglutamine tract...
  27. Li W, Serpell L, Carter W, Rubinsztein D, Huntington J. Expression and characterization of full-length human huntingtin, an elongated HEAT repeat protein. J Biol Chem. 2006;281:15916-22 pubmed
    ..CAG trinucleotide repeats, resulting in a polyglutamine stretch of >37 on the N terminus of the protein huntingtin (htt). htt is a large (347 kDa), ubiquitously expressed protein...
  28. Schilling B, Gafni J, Torcassi C, Cong X, Row R, LaFevre Bernt M, et al. Huntingtin phosphorylation sites mapped by mass spectrometry. Modulation of cleavage and toxicity. J Biol Chem. 2006;281:23686-97 pubmed
    b>Huntingtin (Htt) is a large protein of 3144 amino acids, whose function and regulation have not been well defined. Polyglutamine (polyQ) expansion in the N terminus of Htt causes the neurodegenerative disorder Huntington disease (HD)...
  29. Baldo B, Weiss A, Parker C, Bibel M, Paganetti P, Kaupmann K. A screen for enhancers of clearance identifies huntingtin as a heat shock protein 90 (Hsp90) client protein. J Biol Chem. 2012;287:1406-14 pubmed publisher
    Mechanisms to reduce the cellular levels of mutant huntingtin (mHtt) provide promising strategies for treating Huntington disease (HD)...
  30. Shin J, Fang Z, Yu Z, Wang C, Li S, Li X. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol. 2005;171:1001-12 pubmed
    ..However, little is known about the role of glia in HD neuropathology. Here, we report that mutant huntingtin accumulates in glial nuclei in HD brains and decreases the expression of glutamate transporters...
  31. Zhang Y, Leavitt B, Van Raamsdonk J, Dragatsis I, Goldowitz D, MacDonald M, et al. Huntingtin inhibits caspase-3 activation. EMBO J. 2006;25:5896-906 pubmed
    Huntington's disease results from a mutation in the HD gene encoding for the protein huntingtin. The function of huntingtin, although beginning to be elucidated, remains largely unclear...
  32. Atwal R, Xia J, Pinchev D, Taylor J, Epand R, Truant R. Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Hum Mol Genet. 2007;16:2600-15 pubmed
    Huntington's disease is caused by an expanded polyglutamine tract in huntingtin protein, leading to accumulation of huntingtin in the nuclei of striatal neurons...
  33. Wang N, Gray M, Lu X, Cantle J, Holley S, Greiner E, et al. Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease. Nat Med. 2014;20:536-41 pubmed publisher
    ..neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal ..
  34. Hoffner G, Kahlem P, Djian P. Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with beta-tubulin: relevance to Huntington's disease. J Cell Sci. 2002;115:941-8 pubmed
    Huntington's disease results from an expansion of a series of glutamine repeats in the protein huntingtin. We have discovered from immunopurification studies that huntingtin combines specifically with the beta subunit of tubulin...
  35. Warby S, Chan E, Metzler M, Gan L, Singaraja R, Crocker S, et al. Huntingtin phosphorylation on serine 421 is significantly reduced in the striatum and by polyglutamine expansion in vivo. Hum Mol Genet. 2005;14:1569-77 pubmed
    Huntington disease (HD) results from polyglutamine expansion in the huntingtin protein (htt). Despite the widespread tissue expression pattern of htt, neuronal loss is highly selective to medium spiny neurons of the striatum...
  36. Ciammola A, Sassone J, Alberti L, Meola G, Mancinelli E, Russo M, et al. Increased apoptosis, Huntingtin inclusions and altered differentiation in muscle cell cultures from Huntington's disease subjects. Cell Death Differ. 2006;13:2068-78 pubmed
    Mutated huntingtin (htt) is ubiquitously expressed in tissues of Huntington's disease (HD) patients. In the brain, the mutated protein leads to neuronal cell dysfunction and death, associated with formation of htt-positive inclusions...
  37. Bradford J, Shin J, Roberts M, Wang C, Li X, Li S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A. 2009;106:22480-5 pubmed publisher
    Huntington disease (HD) is an inherited neurological disorder caused by a polyglutamine expansion in the protein huntingtin and is characterized by selective neurodegeneration that preferentially occurs in striatal medium spiny neurons...
  38. Maiuri T, Woloshansky T, Xia J, Truant R. The huntingtin N17 domain is a multifunctional CRM1 and Ran-dependent nuclear and cilial export signal. Hum Mol Genet. 2013;22:1383-94 pubmed publisher
    The first 17 amino acids of Huntington's disease (HD) protein, huntingtin, comprise an amphipathic alpha-helical domain that can target huntingtin to the endoplasmic reticulum (ER)...
  39. Zeron M, Hansson O, Chen N, Wellington C, Leavitt B, Brundin P, et al. Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron. 2002;33:849-60 pubmed
    ..vulnerable to NMDAR-mediated death in a YAC transgenic FVB/N mouse model of HD expressing full-length mutant huntingtin, compared with wild-type FVB/N mice...
  40. Benn C, Landles C, Li H, Strand A, Woodman B, Sathasivam K, et al. Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease. Hum Mol Genet. 2005;14:3065-78 pubmed
    ..However, our data suggest that cytoplasmic mutant exon 1 htt, if present, contributes to disease progression. ..
  41. Seong I, Woda J, Song J, Lloret A, Abeyrathne P, Woo C, et al. Huntingtin facilitates polycomb repressive complex 2. Hum Mol Genet. 2010;19:573-83 pubmed publisher
    Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein...
  42. Yan Y, Peng D, Tian J, Chi J, Tan J, Yin X, et al. Essential sequence of the N-terminal cytoplasmic localization-related domain of huntingtin and its effect on huntingtin aggregates. Sci China Life Sci. 2011;54:342-50 pubmed publisher
    Huntington's disease (HD) is caused by abnormal CAG repeat expansion in the 5'-end of the Huntingtin (HTT) gene...
  43. Kwan W, Träger U, Davalos D, Chou A, Bouchard J, Andre R, et al. Mutant huntingtin impairs immune cell migration in Huntington disease. J Clin Invest. 2012;122:4737-47 pubmed publisher
    ..HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells...
  44. Thakur A, Jayaraman M, Mishra R, Thakur M, Chellgren V, Byeon I, et al. Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism. Nat Struct Mol Biol. 2009;16:380-9 pubmed publisher
    ..We show here that the 17-amino-acid flanking sequence (HTT(NT)) N-terminal to the polyQ in the toxic huntingtin exon 1 fragment imparts onto this peptide a complex alternative aggregation mechanism...
  45. Holbert S, Dedeoglu A, Humbert S, Saudou F, Ferrante R, Neri C. Cdc42-interacting protein 4 binds to huntingtin: neuropathologic and biological evidence for a role in Huntington's disease. Proc Natl Acad Sci U S A. 2003;100:2712-7 pubmed
    Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine (polyQ) expansion in the protein huntingtin (htt)...
  46. Khoshnan A, Ko J, Watkin E, Paige L, Reinhart P, Patterson P. Activation of the IkappaB kinase complex and nuclear factor-kappaB contributes to mutant huntingtin neurotoxicity. J Neurosci. 2004;24:7999-8008 pubmed
    Transcriptional dysregulation by mutant huntingtin (Htt) protein has been implicated in the pathogenesis of Huntington's disease (HD)...
  47. Reijonen S, Putkonen N, Nørremølle A, Lindholm D, Korhonen L. Inhibition of endoplasmic reticulum stress counteracts neuronal cell death and protein aggregation caused by N-terminal mutant huntingtin proteins. Exp Cell Res. 2008;314:950-60 pubmed publisher
    ..We show here that the expression of N-terminal huntingtin proteins with expanded polyglutamine (polyQ) repeats causes cell death in neuronal PC6...
  48. Morfini G, You Y, Pollema S, Kaminska A, Liu K, Yoshioka K, et al. Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat Neurosci. 2009;12:864-71 pubmed publisher
    ..These data identify JNK3 as a critical mediator of polyQ-Htt toxicity and provide a molecular basis for polyQ-Htt-induced inhibition of FAT. ..
  49. Havel L, Wang C, Wade B, Huang B, Li S, Li X. Preferential accumulation of N-terminal mutant huntingtin in the nuclei of striatal neurons is regulated by phosphorylation. Hum Mol Genet. 2011;20:1424-37 pubmed publisher
    An expanded polyglutamine tract (>37 glutamines) in the N-terminal region of huntingtin (htt) causes htt to accumulate in the nucleus, leading to transcriptional dysregulation in Huntington disease (HD)...
  50. Reiner A, Del Mar N, Deng Y, Meade C, Sun Z, Goldowitz D. R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice. J Comp Neurol. 2007;505:603-29 pubmed
    ..while cortical and striatal neurons can survive nearly a year with nuclear and extranuclear aggregates of mutant huntingtin, such lengthy survival does reveal cortical and striatal abnormality brought on by the truncated mutant protein.
  51. Colin E, Zala D, Liot G, Rangone H, Borrell Pages M, Li X, et al. Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J. 2008;27:2124-34 pubmed publisher
    ..However, the mechanisms that determine the directionality of transport remain unclear. Huntingtin, the protein mutated in Huntington's disease, is a positive regulatory factor for vesicular transport...
  52. Gu X, Greiner E, Mishra R, Kodali R, Osmand A, Finkbeiner S, et al. Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice. Neuron. 2009;64:828-40 pubmed publisher
    The N-terminal 17 amino acids of huntingtin (NT17) can be phosphorylated on serines 13 and 16; however, the significance of these modifications in Huntington's disease pathogenesis remains unknown...
  53. Dong G, Callegari E, Gloeckner C, Ueffing M, Wang H. Mass spectrometric identification of novel posttranslational modification sites in Huntingtin. Proteomics. 2012;12:2060-4 pubmed publisher
    Huntington's disease (HD) is caused by a CAG triplet repeat expansion in exon 1 of the Huntingtin (Htt) gene, encoding an abnormal expanded polyglutamine (polyQ) tract that confers toxicity to the mutant Htt (mHtt) protein...
  54. Djousse L, Knowlton B, Hayden M, Almqvist E, Brinkman R, Ross C, et al. Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease. Am J Med Genet A. 2003;119A:279-82 pubmed
    ..These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats. ..
  55. del Toro D, Canals J, Gines S, Kojima M, Egea G, Alberch J. Mutant huntingtin impairs the post-Golgi trafficking of brain-derived neurotrophic factor but not its Val66Met polymorphism. J Neurosci. 2006;26:12748-57 pubmed
    ..In view of these data and the involvement of huntingtin in intracellular trafficking, we examined the intracellular transport and release of Val66Val BDNF (Val-BDNF) ..
  56. Quarrell O, Rigby A, Barron L, Crow Y, Dalton A, Dennis N, et al. Reduced penetrance alleles for Huntington's disease: a multi-centre direct observational study. J Med Genet. 2007;44:e68 pubmed
    ..When DNA results are in this range, a conservative approach is to say that there is at least a 40% chance the person will be asymptomatic at age 65 years and at least a 30% chance the person will be asymptomatic at age 75 years. ..
  57. Kaytor M, Wilkinson K, Warren S. Modulating huntingtin half-life alters polyglutamine-dependent aggregate formation and cell toxicity. J Neurochem. 2004;89:962-73 pubmed
    ..To investigate the mechanism of aggregate formation, we have developed a cell culture model to express huntingtin designed to have an altered degradation rate through the ubiquitin-dependent N-end rule pathway...
  58. Godin J, Colombo K, Molina Calavita M, Keryer G, Zala D, Charrin B, et al. Huntingtin is required for mitotic spindle orientation and mammalian neurogenesis. Neuron. 2010;67:392-406 pubmed publisher
    b>Huntingtin is the protein mutated in Huntington's disease, a devastating neurodegenerative disorder. We demonstrate here that huntingtin is essential to control mitosis. Huntingtin is localized at spindle poles during mitosis...
  59. Crook Z, Housman D. Huntington's disease: can mice lead the way to treatment?. Neuron. 2011;69:423-35 pubmed publisher
    ..degeneration and rarity of intranuclear inclusions in HD, and the fact that mice expressing full-length mutant huntingtin do not demonstrate a shortened life span characteristic of HD...
  60. Klempíř J, Zidovska J, Stochl J, Ing V, Uhrová T, Roth J. The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease. Mov Disord. 2011;26:125-9 pubmed publisher
    ..3, which results in elongated glutamine tract of huntingtin. The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and ..
  61. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet. 2003;35:76-83 pubmed
    b>Huntingtin protein is mutated in Huntington disease. We previously reported that wild-type but not mutant huntingtin stimulates transcription of the gene encoding brain-derived neurotrophic factor (BDNF; ref. 2)...
  62. Graham R, Deng Y, Slow E, Haigh B, Bissada N, Lu G, et al. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell. 2006;125:1179-91 pubmed
    Cleavage of huntingtin (htt) has been characterized in vitro, and accumulation of caspase cleavage fragments represents an early pathological change in brains of Huntington's disease (HD) patients...
  63. Pouladi M, Xie Y, Skotte N, Ehrnhoefer D, Graham R, Kim J, et al. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. Hum Mol Genet. 2010;19:1528-38 pubmed publisher
    Levels of full-length huntingtin (FL htt) influence organ and body weight, independent of polyglutamine length...
  64. Hermel E, Gafni J, Propp S, Leavitt B, Wellington C, Young J, et al. Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease. Cell Death Differ. 2004;11:424-38 pubmed
    ..Proteolytic processing of full-length mutant huntingtin (Htt) and subsequent events may play an important role in the selective neuronal cell death found in this ..
  65. Rockabrand E, Slepko N, Pantalone A, Nukala V, Kazantsev A, Marsh J, et al. The first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis. Hum Mol Genet. 2007;16:61-77 pubmed
    ..Interestingly, neither mitochondrial nor ER associations seem to be required to promote long-term [Ca2+]i dyshomeostasis. ..
  66. Omi K, Hachiya N, Tanaka M, Tokunaga K, Kaneko K. 14-3-3zeta is indispensable for aggregate formation of polyglutamine-expanded huntingtin protein. Neurosci Lett. 2008;431:45-50 pubmed
    ..an autosomal dominant progressive neurodegenerative disorder caused by polyglutamine (polyQ) expansions in the huntingtin (Htt) protein...
  67. Khoshnan A, Ko J, Tescu S, Brundin P, Patterson P. IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtin. PLoS ONE. 2009;4:e5768 pubmed publisher
    Proteolysis of huntingtin (Htt) plays a key role in the pathogenesis of Huntington's disease (HD). However, the environmental cues and signaling pathways that regulate Htt proteolysis are poorly understood...
  68. Simpson J, Gil Mohapel J, Pouladi M, Ghilan M, Xie Y, Hayden M, et al. Altered adult hippocampal neurogenesis in the YAC128 transgenic mouse model of Huntington disease. Neurobiol Dis. 2011;41:249-60 pubmed publisher
    ..In this study, we demonstrate decreases in neurogenesis in the DG of YAC128 mice, and these deficits may contribute to the cognitive abnormalities observed in these animals. ..
  69. Nucifora L, Burke K, Feng X, Arbez N, Zhu S, Miller J, et al. Identification of novel potentially toxic oligomers formed in vitro from mammalian-derived expanded huntingtin exon-1 protein. J Biol Chem. 2012;287:16017-28 pubmed publisher
    ..disorder that arises from an expanded polyglutamine region in the N terminus of the HD gene product, huntingtin. Protein inclusions comprised of N-terminal fragments of mutant huntingtin are a characteristic feature of ..
  70. Behrens P, Franz P, Woodman B, Lindenberg K, Landwehrmeyer G. Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation. Brain. 2002;125:1908-22 pubmed
    ..alterations in brain glutamate handling we studied transgenic mice expressing an N-terminal fragment of mutant huntingtin (R6/2)...
  71. Strehlow A, Li J, Myers R. Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space. Hum Mol Genet. 2007;16:391-409 pubmed
    ..CAG trinucleotide repeat in the first exon of the HD gene, which results in a toxic polyglutamine stretch within huntingtin, the protein it encodes...
  72. Wheeler V, Persichetti F, McNeil S, Mysore J, Mysore S, MacDonald M, et al. Factors associated with HD CAG repeat instability in Huntington disease. J Med Genet. 2007;44:695-701 pubmed
    ..Significant sibling-sibling correlation for repeat instability suggests that genetic factors play a role in intergenerational CAG repeat instability. ..
  73. Trushina E, Heldebrant M, Perez Terzic C, Bortolon R, Kovtun I, Badger J, et al. Microtubule destabilization and nuclear entry are sequential steps leading to toxicity in Huntington's disease. Proc Natl Acad Sci U S A. 2003;100:12171-6 pubmed
    ..toxic peptide theory posits that N-terminal cleavage fragments of mutant Huntington's disease protein [mutant huntingtin (mhtt)] enter the nucleus to cause transcriptional dysfunction...
  74. Fan J, Cowan C, Zhang L, Hayden M, Raymond L. Interaction of postsynaptic density protein-95 with NMDA receptors influences excitotoxicity in the yeast artificial chromosome mouse model of Huntington's disease. J Neurosci. 2009;29:10928-38 pubmed publisher
    ..chromosome (YAC) transgenic mouse model expressing polyglutamine (polyQ)-expanded (mutant) full-length human huntingtin (htt)...
  75. Zhang Q, Yeh T, Leyva A, Frank L, Miller J, Kim Y, et al. A compact beta model of huntingtin toxicity. J Biol Chem. 2011;286:8188-96 pubmed publisher
    Huntington disease results from an expanded polyglutamine region in the N terminus of the huntingtin protein...
  76. Hatters D. Putting huntingtin "aggregation" in view with windows into the cellular milieu. Curr Top Med Chem. 2012;12:2611-22 pubmed
    ..Finally, discussion centers on strategies forward to improve our knowledge for how aggregation relates to cellular dysfunction. ..
  77. Gil J, Mohapel P, Araújo I, Popovic N, Li J, Brundin P, et al. Reduced hippocampal neurogenesis in R6/2 transgenic Huntington's disease mice. Neurobiol Dis. 2005;20:744-51 pubmed
    ..Reduced hippocampal neurogenesis may be a novel neuropathological feature in R6/2 mice that could be assessed when evaluating potential therapies. ..
  78. Kuhn A, Goldstein D, Hodges A, Strand A, Sengstag T, Kooperberg C, et al. Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum Mol Genet. 2007;16:1845-61 pubmed
    To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of ..
  79. Noh J, Lee H, Song S, Kim N, Im W, Kim M, et al. SCAMP5 links endoplasmic reticulum stress to the accumulation of expanded polyglutamine protein aggregates via endocytosis inhibition. J Biol Chem. 2009;284:11318-25 pubmed publisher
    ..expression of SCAMP5 augments the formation of ubiquitin-positive and detergent-resistant aggregates of mutant huntingtin (mtHTT)...
  80. Kelley N, Huang X, Tam S, Spiess C, Frydman J, Pande V. The predicted structure of the headpiece of the Huntingtin protein and its implications on Huntingtin aggregation. J Mol Biol. 2009;388:919-27 pubmed publisher
    ..performed simulated tempering molecular dynamics simulations to study the thermodynamics of the headpiece of the Huntingtin (Htt) protein (N17(Htt))...
  81. Keryer G, Pineda J, Liot G, Kim J, Dietrich P, Benstaali C, et al. Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease. J Clin Invest. 2011;121:4372-82 pubmed publisher
    ..It is caused by expansion of a CAG repeat in the first exon of the huntingtin (HTT) gene that encodes a mutant HTT protein with a polyglutamine (polyQ) expansion at the amino terminus...
  82. Bugg C, Isas J, Fischer T, Patterson P, Langen R. Structural features and domain organization of huntingtin fibrils. J Biol Chem. 2012;287:31739-46 pubmed publisher
    Misfolding and aggregation of huntingtin is one of the hallmarks of Huntington disease, but the overall structure of these aggregates and the mechanisms by which huntingtin misfolds remain poorly understood...
  83. Cui X, Liang Q, Liang Y, Lu M, Ding Y, Lu B. TR-FRET assays of Huntingtin protein fragments reveal temperature and polyQ length-dependent conformational changes. Sci Rep. 2014;4:5601 pubmed publisher
    ..One of the well established examples is the TR-FRET assay for mutant huntingtin protein (HTT), which is the major cause of the neurodegenerative Huntington's disease (HD)...
  84. Iwata A, Riley B, Johnston J, Kopito R. HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem. 2005;280:40282-92 pubmed
    ..These data suggest that HDAC6-dependent retrograde transport on microtubules is used by cells to increase the efficiency and selectivity of autophagic degradation. ..
  85. Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 2005;171:603-14 pubmed
    ..Strikingly, p62 and LC3 formed a shell surrounding aggregates of mutant huntingtin. Reduction of p62 protein levels or interference with p62 function significantly increased cell death that was ..
  86. Zuchner T, Brundin P. Mutant huntingtin can paradoxically protect neurons from death. Cell Death Differ. 2008;15:435-42 pubmed
    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a mutation in the gene huntingtin and characterized by motor, cognitive and psychiatric symptoms. Huntingtin contains a CAG repeat in exon 1...
  87. Wang H, Lim P, Karbowski M, Monteiro M. Effects of overexpression of huntingtin proteins on mitochondrial integrity. Hum Mol Genet. 2009;18:737-52 pubmed publisher
    ..disease (HD) is caused by an expansion of a CAG trinucleotide sequence that encodes a polyglutamine tract in the huntingtin (Htt) protein...
  88. Thompson L, Aiken C, Kaltenbach L, Agrawal N, Illes K, Khoshnan A, et al. IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. J Cell Biol. 2009;187:1083-99 pubmed publisher
    Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons...
  89. Peters Libeu C, Miller J, Rutenber E, Newhouse Y, Krishnan P, Cheung K, et al. Disease-associated polyglutamine stretches in monomeric huntingtin adopt a compact structure. J Mol Biol. 2012;421:587-600 pubmed publisher
    ..In Huntington's disease, tracts longer than 36 glutamines in the protein huntingtin (htt) cause degeneration...
  90. Singaraja R, Hadano S, Metzler M, Givan S, Wellington C, Warby S, et al. HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis. Hum Mol Genet. 2002;11:2815-28 pubmed
    Huntington disease (HD) is caused by polyglutamine [poly(Q)] expansion in the protein huntingtin (htt)...