huntingtin

Summary

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

Top Publications

  1. 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...
  2. 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)...
  3. 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...
  4. 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)...
  5. 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...
  6. 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...
  7. 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 ..
  8. 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...
  9. 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)...

More Information

Publications109 found, 100 shown here

  1. 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)...
  2. 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...
  3. 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...
  4. 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...
  5. 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 ..
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. 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)...
  11. 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...
  12. 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. ..
  13. 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...
  14. 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...
  15. 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...
  16. 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...
  17. 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)...
  18. 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)...
  19. 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...
  20. 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. ..
  21. 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)...
  22. 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.
  23. 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...
  24. 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...
  25. 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...
  26. 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. ..
  27. 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) ..
  28. 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. ..
  29. 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...
  30. 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...
  31. 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...
  32. 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 ..
  33. 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)...
  34. 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...
  35. 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...
  36. 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 ..
  37. 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. ..
  38. 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...
  39. 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...
  40. 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. ..
  41. 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 ..
  42. 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)...
  43. 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...
  44. 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. ..
  45. 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...
  46. 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)...
  47. 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...
  48. 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. ..
  49. 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. ..
  50. 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 ..
  51. 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)...
  52. 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))...
  53. 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...
  54. 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...
  55. 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)...
  56. 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. ..
  57. 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 ..
  58. 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...
  59. 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...
  60. 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...
  61. 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...
  62. 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)...
  63. Majumder P, Raychaudhuri S, Chattopadhyay B, Bhattacharyya N. Increased caspase-2, calpain activations and decreased mitochondrial complex II activity in cells expressing exogenous huntingtin exon 1 containing CAG repeat in the pathogenic range. Cell Mol Neurobiol. 2007;27:1127-45 pubmed
    ..dominant neurodegenerative disease caused by the expansion of polymorphic CAG repeats beyond 36 at exon 1 of huntingtin gene (htt)...
  64. Orr A, Li S, Wang C, Li H, Wang J, Rong J, et al. N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J Neurosci. 2008;28:2783-92 pubmed publisher
    Huntington's disease (HD) is caused by polyglutamine (polyQ) expansion in huntingtin (htt), a large (350 kDa) protein that localizes predominantly to the cytoplasm...
  65. Tam S, Spiess C, Auyeung W, Joachimiak L, Chen B, Poirier M, et al. The chaperonin TRiC blocks a huntingtin sequence element that promotes the conformational switch to aggregation. Nat Struct Mol Biol. 2009;16:1279-85 pubmed publisher
    ..Molecular chaperones modulate the aggregation and toxicity of the huntingtin (Htt) protein by an ill-defined mechanism. Here we determine how the chaperonin TRiC suppresses Htt aggregation...
  66. Williamson T, Vitalis A, Crick S, Pappu R. Modulation of polyglutamine conformations and dimer formation by the N-terminus of huntingtin. J Mol Biol. 2010;396:1295-309 pubmed publisher
    ..and circular dichroism experiments that quantify the effect of the N-terminal 17-residue (Nt17) segment of the huntingtin protein on polyglutamine conformations and intermolecular interactions...
  67. Zheng Z, Li A, Holmes B, Marasa J, Diamond M. An N-terminal nuclear export signal regulates trafficking and aggregation of Huntingtin (Htt) protein exon 1. J Biol Chem. 2013;288:6063-71 pubmed publisher
    ..is a dominantly inherited neurodegenerative condition caused by polyglutamine expansion in the N terminus of the huntingtin protein (Htt). The first 17 amino acids (N17) of Htt play a key role in regulating its toxicity and aggregation...
  68. Luo S, Vacher C, Davies J, Rubinsztein D. Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity. J Cell Biol. 2005;169:647-56 pubmed
    ..Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract in the huntingtin (htt) protein...
  69. Chang D, Rintoul G, Pandipati S, Reynolds I. Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis. 2006;22:388-400 pubmed
    Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine repeat in the huntingtin gene (Htt). Mitochondrial defects and protein aggregates are characteristic of affected neurons...
  70. Aiken C, Steffan J, Guerrero C, Khashwji H, Lukacsovich T, Simmons D, et al. Phosphorylation of threonine 3: implications for Huntingtin aggregation and neurotoxicity. J Biol Chem. 2009;284:29427-36 pubmed publisher
    b>Huntingtin (Htt) is a widely expressed protein that causes tissue-specific degeneration when mutated to contain an expanded polyglutamine (poly(Q)) domain...
  71. Leitman J, Ulrich Hartl F, Lederkremer G. Soluble forms of polyQ-expanded huntingtin rather than large aggregates cause endoplasmic reticulum stress. Nat Commun. 2013;4:2753 pubmed publisher
    ..However, growing evidence implicates soluble oligomeric polyglutamine-expanded huntingtin in cytotoxicity...
  72. Choo Y, Johnson G, MacDonald M, Detloff P, Lesort M. Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum Mol Genet. 2004;13:1407-20 pubmed
    Huntington's disease (HD) is initiated by an abnormally expanded polyglutamine stretch in the huntingtin protein, conferring a novel property on the protein that leads to the loss of striatal neurons...
  73. Sahlender D, Roberts R, Arden S, Spudich G, Taylor M, Luzio J, et al. Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis. J Cell Biol. 2005;169:285-95 pubmed
    ..Two further binding partners for optineurin have been identified: huntingtin and Rab8...
  74. Aziz N, Jurgens C, Landwehrmeyer G, van Roon Mom W, van Ommen G, Stijnen T, et al. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease. Neurology. 2009;73:1280-5 pubmed publisher
    ..The underlying mechanism may involve interaction of the polyglutamine domains of normal and mutant huntingtin (fragments) and needs further elucidation...
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    Presymptomatic individuals with the Huntingtin (HTT) CAG expansion mutation that causes Huntington's disease may have higher levels of depressive symptoms than healthy comparison populations...
  76. Culver B, Savas J, Park S, Choi J, Zheng S, Zeitlin S, et al. Proteomic analysis of wild-type and mutant huntingtin-associated proteins in mouse brains identifies unique interactions and involvement in protein synthesis. J Biol Chem. 2012;287:21599-614 pubmed publisher
    Huntington disease is a neurodegenerative disorder caused by a CAG repeat amplification in the gene huntingtin (HTT) that is reflected by a polyglutamine expansion in the Htt protein...
  77. Ratovitski T, Chighladze E, Arbez N, Boronina T, Herbrich S, Cole R, et al. Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis. Cell Cycle. 2012;11:2006-21 pubmed publisher
    ..is a neurodegenerative disorder caused by an expansion of a polyglutamine repeat within the HD gene product, huntingtin. Huntingtin, a large (347 kDa) protein containing multiple HEAT repeats, acts as a scaffold for protein-protein ..
  78. Lunkes A, Lindenberg K, Ben Haïem L, Weber C, Devys D, Landwehrmeyer G, et al. Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol Cell. 2002;10:259-69 pubmed
    Proteolytic processing of mutant huntingtin (mhtt) is regarded as a key event in the pathogenesis of Huntington's disease (HD)...
  79. Anne S, Saudou F, Humbert S. Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced by DNA damage and regulates wild-type and mutant huntingtin toxicity in neurons. J Neurosci. 2007;27:7318-28 pubmed
    b>Huntingtin is an antiapoptotic protein that becomes toxic when its polyglutamine stretch is expanded, resulting in Huntington's disease (HD). Protein context and posttranslational modifications regulate huntingtin toxicity...
  80. Raychaudhuri S, Sinha M, Mukhopadhyay D, Bhattacharyya N. HYPK, a Huntingtin interacting protein, reduces aggregates and apoptosis induced by N-terminal Huntingtin with 40 glutamines in Neuro2a cells and exhibits chaperone-like activity. Hum Mol Genet. 2008;17:240-55 pubmed
    Expansion of polymorphic glutamine (Q) numbers present at the protein Huntingtin (Htt) beyond 36Q results in its misfolding and aggregation, and the aggregates recruit several other proteins...
  81. Nekooki Machida Y, Kurosawa M, Nukina N, Ito K, Oda T, Tanaka M. Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity. Proc Natl Acad Sci U S A. 2009;106:9679-84 pubmed publisher
    ..Here we show that huntingtin-exon1 (thtt) with expanded polyglutamines remarkably misfolds into distinct amyloid conformations under ..
  82. Kim M, Chelliah Y, Kim S, Otwinowski Z, Bezprozvanny I. Secondary structure of Huntingtin amino-terminal region. Structure. 2009;17:1205-12 pubmed publisher
    ..neurodegenerative disorder resulting from polyglutamine (polyQ) expansion (>36Q) within the first exon of Huntingtin (Htt) protein...
  83. Jayaraman M, Kodali R, Sahoo B, Thakur A, Mayasundari A, Mishra R, et al. Slow amyloid nucleation via ?-helix-rich oligomeric intermediates in short polyglutamine-containing huntingtin fragments. J Mol Biol. 2012;415:881-99 pubmed publisher
    ..segment (htt(NT)) that leads into the polyglutamine (polyQ) segment in the Huntington's disease protein huntingtin (htt) dramatically increases aggregation rates and changes the aggregation mechanism, compared to a simple polyQ ..
  84. Kim M. Beta conformation of polyglutamine track revealed by a crystal structure of Huntingtin N-terminal region with insertion of three histidine residues. Prion. 2013;7:221-8 pubmed publisher
    ..neurodegenerative disorder caused by a polyglutamine (polyQ) expansion (> 35Q) in the first exon (EX1) of huntingtin protein (Htt)...
  85. Bae B, Xu H, Igarashi S, Fujimuro M, Agrawal N, Taya Y, et al. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron. 2005;47:29-41 pubmed
    ..Mutant huntingtin (mHtt) with expanded polyglutamine (polyQ) binds to p53 and upregulates levels of nuclear p53 as well as p53 ..
  86. Kegel K, Sapp E, Yoder J, Cuiffo B, Sobin L, Kim Y, et al. Huntingtin associates with acidic phospholipids at the plasma membrane. J Biol Chem. 2005;280:36464-73 pubmed
    We have identified a domain in the N terminus of huntingtin that binds to membranes...