Genomes and Genes
Gene Symbol: Ccnd2
Description: cyclin D2
Alias: 2600016F06Rik, AI256817, BF642806, C86853, Vin-1, Vin1, cD2, G1/S-specific cyclin-D2
- Matsushime H, Roussel M, Ashmun R, Sherr C. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell. 1991;65:701-13 pubmed..The timing of p36CYL expression, its rapid turnover in the absence of CSF-1, and its phosphorylation and transient binding to a cdc2-related polypeptide suggest that CYL genes may function during S phase commitment. ..
- Kushner J, Ciemerych M, Sicinska E, Wartschow L, Teta M, Long S, et al. Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth. Mol Cell Biol. 2005;25:3752-62 pubmed..Thus, cyclins D2 and D1 were essential for beta-cell expansion in adult mice. Strategies to tightly regulate D-type cyclin activity in beta cells could prevent or cure diabetes. ..
- Pasumarthi K, Nakajima H, Nakajima H, Soonpaa M, Field L. Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice. Circ Res. 2005;96:110-8 pubmed..These data suggested that modulation of D-type cyclins could be exploited to promote regenerative growth in injured hearts. ..
- Wianny F, Real F, Mummery C, van Rooijen M, Lahti J, Samarut J, et al. G1-phase regulators, cyclin D1, cyclin D2, and cyclin D3: up-regulation at gastrulation and dynamic expression during neurulation. Dev Dyn. 1998;212:49-62 pubmed..In the hindbrain, cyclin D1 and D2 show distinct segment-specific restricted expression and this pattern is conserved between mouse and chick. These results strongly suggest that D-type cyclins act as developmental regulators. ..
- Jirawatnotai S, Hu Y, Michowski W, Elias J, Becks L, Bienvenu F, et al. A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature. 2011;474:230-4 pubmed publisher....
- Bienvenu F, Jirawatnotai S, Elias J, Meyer C, Mizeracka K, Marson A, et al. Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature. 2010;463:374-8 pubmed publisher..Our approach, which we term 'genetic-proteomic', can be used to study the in vivo function of essentially any protein. ..
- Ai D, Fu X, Wang J, Lu M, Chen L, Baldini A, et al. Canonical Wnt signaling functions in second heart field to promote right ventricular growth. Proc Natl Acad Sci U S A. 2007;104:9319-24 pubmed..Our findings reveal that Wnt signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium. ..
- Bicknell K, Coxon C, Brooks G. Can the cardiomyocyte cell cycle be reprogrammed?. J Mol Cell Cardiol. 2007;42:706-21 pubmed..The validity of therapeutic strategies that aim to reinstate the proliferative potential of cardiomyocytes to improve myocardial repair following injury will be discussed. ..
- Kowalczyk A, Filipkowski R, Rylski M, Wilczynski G, Konopacki F, Jaworski J, et al. The critical role of cyclin D2 in adult neurogenesis. J Cell Biol. 2004;167:209-13 pubmed..We describe herein that adult mice mutated in the cell cycle regulatory gene Ccnd2, encoding cyclin D2, lack newly born neurons in both of these brain structures...
- Georgia S, Bhushan A. Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J Clin Invest. 2004;114:963-8 pubmed....
- Pu W, Ishiwata T, Juraszek A, Ma Q, Izumo S. GATA4 is a dosage-sensitive regulator of cardiac morphogenesis. Dev Biol. 2004;275:235-44 pubmed..These data demonstrate that multiple aspects of embryonic cardiac morphogenesis and function are exquisitely sensitive to small changes in GATA4 expression levels. ..
- Denicourt C, Kozak C, Rassart E. Gris1, a new common integration site in Graffi murine leukemia virus-induced leukemias: overexpression of a truncated cyclin D2 due to alternative splicing. J Virol. 2003;77:37-44 pubmed..1-kb transcript from the cyclin D2 gene that encodes a truncated cyclin D2 of 17 kDa. The expression of this 1.1-kb transcript is specific to tumors in which Gris1 is rearranged but is also detected at low levels in normal tissue. ..
- Yamak A, Temsah R, Maharsy W, Caron S, Paradis P, Aries A, et al. Cyclin D2 rescues size and function of GATA4 haplo-insufficient hearts. Am J Physiol Heart Circ Physiol. 2012;303:H1057-66 pubmed publisher..Search for GATA4 targets/effectors revealed cyclin D(2) (CD2), a member of the D-type cyclins (D(1), D(2), and D(3)) that play a vital role in cell growth and differentiation ..
- Glickstein S, Monaghan J, Koeller H, Jones T, Ross M. Cyclin D2 is critical for intermediate progenitor cell proliferation in the embryonic cortex. J Neurosci. 2009;29:9614-24 pubmed publisherExpression of cyclins D1 (cD1) and D2 (cD2) in ventricular zone and subventricular zone (SVZ), respectively, suggests that a switch to cD2 could be a requisite step in the generation of cortical intermediate progenitor cells (IPCs)...
- Inaba T, Matsushime H, Valentine M, Roussel M, Sherr C, Look A. Genomic organization, chromosomal localization, and independent expression of human cyclin D genes. Genomics. 1992;13:565-74 pubmed..The human cyclin D1 gene (approved gene symbol, CCND1) was assigned to chromosome band 11q13, cyclin D2 (CCND2) to chromosome band 12p13, and cyclin D3 (CCND3) to chromosome band 6p21...
- Kozar K, Ciemerych M, Rebel V, Shigematsu H, Zagozdzon A, Sicinska E, et al. Mouse development and cell proliferation in the absence of D-cyclins. Cell. 2004;118:477-91 pubmed..Lastly, we found that cells lacking D-cyclins display reduced susceptibility to the oncogenic transformation. Our results reveal the presence of alternative mechanisms that allow cell cycle progression in a cyclin D-independent fashion. ..
- Meyyappan M, Wong H, Hull C, Riabowol K. Increased expression of cyclin D2 during multiple states of growth arrest in primary and established cells. Mol Cell Biol. 1998;18:3163-72 pubmed....
- Zeisberg E, Ma Q, Juraszek A, Moses K, Schwartz R, Izumo S, et al. Morphogenesis of the right ventricle requires myocardial expression of Gata4. J Clin Invest. 2005;115:1522-31 pubmed..Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal. ..
- Fatrai S, Elghazi L, Balcazar N, Cras Méneur C, Krits I, Kiyokawa H, et al. Akt induces beta-cell proliferation by regulating cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 activity. Diabetes. 2006;55:318-25 pubmed..These data also indicate that alteration in levels of these cell cycle components could affect the maintenance of beta-cell mass in basal states and the adaptation of beta-cells to pathological states resulting in diabetes. ..
- Cooper A, Sawai C, Sicinska E, Powers S, Sicinski P, Clark M, et al. A unique function for cyclin D3 in early B cell development. Nat Immunol. 2006;7:489-97 pubmed..Here, analysis of Ccnd1(-/-), Ccnd2(-/-), Ccnd3(-/-) and Ccnd2(-/-)Ccnd3(-/-) mice showed that cyclin D3 was uniquely required for the development of ..
- Ciemerych M, Kenney A, Sicinska E, Kalaszczynska I, Bronson R, Rowitch D, et al. Development of mice expressing a single D-type cyclin. Genes Dev. 2002;16:3277-89 pubmed..Hence, the requirement for a particular cyclin in a given tissue is likely caused by specific transcription factors, rather than by unique properties of cyclins. ..
- Ben Abdallah N, Filipkowski R, Pruschy M, Jaholkowski P, Winkler J, Kaczmarek L, et al. Impaired long-term memory retention: common denominator for acutely or genetically reduced hippocampal neurogenesis in adult mice. Behav Brain Res. 2013;252:275-86 pubmed publisher..In contrast, spatial long-term memory retention is consistently altered after both approaches suggesting a plausible implication of hippocampal neurogenesis in this cognitive process. ..
- Lyons I, Parsons L, Hartley L, Li R, Andrews J, Robb L, et al. Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. Genes Dev. 1995;9:1654-66 pubmed..The data demonstrate that Nkx2-5 is essential for normal heart morphogenesis, myogenesis, and function. Furthermore, this gene is a component of a genetic pathway required for myogenic specialization of the ventricles. ..
- Sicinski P, Donaher J, Geng Y, Parker S, Gardner H, Park M, et al. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature. 1996;384:470-4 pubmed..The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA. ..
- Susaki E, Nakayama K, Nakayama K. Cyclin D2 translocates p27 out of the nucleus and promotes its degradation at the G0-G1 transition. Mol Cell Biol. 2007;27:4626-40 pubmed..These results indicate that cyclin D2 translocates p27 from the nucleus into the cytoplasm for its KPC-dependent degradation at the G(0)-G(1) transition. ..
- Xiong Y, Menninger J, Beach D, Ward D. Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins. Genomics. 1992;13:575-84 pubmed..We now report the molecular cloning of two additional human D-type cyclin genes, CCND2 (cyclin D2) and CCND3 (cyclin D3)...
- Denicourt C, Legault P, McNabb F, Rassart E. Human and mouse cyclin D2 splice variants: transforming activity and subcellular localization. Oncogene. 2008;27:1253-62 pubmed..Interestingly, the presence of a similar, alternatively spliced cyclin D2 mRNA was also detected in some human brain tumors. ..
- Glickstein S, Alexander S, Ross M. Differences in cyclin D2 and D1 protein expression distinguish forebrain progenitor subsets. Cereb Cortex. 2007;17:632-42 pubmed..Among the cell cycle proteins, understanding of the relative roles of the G1-phase active cyclins D2 and D1 (cD2 and cD1) has been hampered by lack of data regarding their expression patterns...
- Rojas A, Kong S, Agarwal P, Gilliss B, Pu W, Black B. GATA4 is a direct transcriptional activator of cyclin D2 and Cdk4 and is required for cardiomyocyte proliferation in anterior heart field-derived myocardium. Mol Cell Biol. 2008;28:5420-31 pubmed publisher..These findings establish Cyclin D2 and Cdk4 as direct transcriptional targets of GATA4 and support a model in which GATA4 controls cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes. ..
- Zhong W, Mao S, Tobis S, Angelis E, Jordan M, Roos K, et al. Hypertrophic growth in cardiac myocytes is mediated by Myc through a Cyclin D2-dependent pathway. EMBO J. 2006;25:3869-79 pubmed..These data suggest that Myc is required for a normal hypertrophic response and that its growth-promoting effects are also mediated through a CycD2-dependent pathway. ..
- Escamilla Hernandez R, Chakrabarti R, Romano R, Smalley K, Zhu Q, Lai W, et al. Genome-wide search identifies Ccnd2 as a direct transcriptional target of Elf5 in mouse mammary gland. BMC Mol Biol. 2010;11:68 pubmed publisher..Here we focus on one putative target of Elf5, the Ccnd2 gene that appeared in our screen...
- Raetzman L, Cai J, Camper S. Hes1 is required for pituitary growth and melanotrope specification. Dev Biol. 2007;304:455-66 pubmed..These results demonstrate that Notch signaling plays multiple roles in pituitary development, influencing precursor number, organ size, cell differentiation and ultimately cell fate. ..
- Knoepfler P, Cheng P, Eisenman R. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev. 2002;16:2699-712 pubmed..Its effects on proliferation and differentiation appear due, at least in part, to down-regulation of a specific subset of cyclin-dependent kinase inhibitors. ..
- Chen L, Fulcoli F, Ferrentino R, Martucciello S, Illingworth E, Baldini A. Transcriptional control in cardiac progenitors: Tbx1 interacts with the BAF chromatin remodeling complex and regulates Wnt5a. PLoS Genet. 2012;8:e1002571 pubmed publisher..We speculate that this may be a general mechanism of T-box function and that Baf60a is a key component of the transcriptional control in cardiac progenitors. ..
- Kashiwagi A, Schipani E, Fein M, Greer P, Shimada M. Targeted deletion of Capn4 in cells of the chondrocyte lineage impairs chondrocyte proliferation and differentiation. Mol Cell Biol. 2010;30:2799-810 pubmed publisher..Collectively, our findings suggest that the calpain small subunit is essential for proper chondrocyte functions in embryonic growth plates. ..
- Nieuwenhuis E, Motoyama J, Barnfield P, Yoshikawa Y, Zhang X, Mo R, et al. Mice with a targeted mutation of patched2 are viable but develop alopecia and epidermal hyperplasia. Mol Cell Biol. 2006;26:6609-22 pubmed..While functional compensation by Ptc1 might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2 function is required for adult skin homeostasis. ..
- Rutter M, Wang J, Huang Z, Kuliszewski M, Post M. Gli2 influences proliferation in the developing lung through regulation of cyclin expression. Am J Respir Cell Mol Biol. 2010;42:615-25 pubmed publisher..However, no change in the levels of cyclins D1, D2, or E1 due to altered Gli3 was observed. These findings suggest that Gli2 and not Gli3 is the primary mediator of Shh signaling influencing fetal lung growth through cyclin regulation. ..
- Holmberg J, Ingner G, Johansson C, Leander P, Hjalt T. PITX2 gain-of-function induced defects in mouse forelimb development. BMC Dev Biol. 2008;8:25 pubmed publisher..Taken together, the tendon, muscle, and bone anomalies further support a role of Pitx2 in forelimb development and may also shed light on the interaction between the skeletal elements and muscles of the limb during embryogenesis. ..
- Shin H, Kim S, Lee H, Choi H. The soluble glucocorticoid-induced tumor necrosis factor receptor causes cell cycle arrest and apoptosis in murine macrophages. Biochem Biophys Res Commun. 2004;316:24-32 pubmed..These findings suggest that sGITR arrests division of the macrophages in G1 by lowering the activities of cdk2 and cdk4, and that this leads to apoptosis. ..
- Matsui T, Kinoshita T, Hirano T, Yokota T, Miyajima A. STAT3 down-regulates the expression of cyclin D during liver development. J Biol Chem. 2002;277:36167-73 pubmed..Thus, STAT3-mediated down-regulation of cyclin D expression is rather specific to fetal hepatocytes that are undergoing maturation processes including a reduction of their proliferation potential. ..
- Geng Y, Yu Q, Sicinska E, Das M, Bronson R, Sicinski P. Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice. Proc Natl Acad Sci U S A. 2001;98:194-9 pubmed..Here we report that ablation of p27(Kip1) restores essentially normal development in cyclin D1-deficient mice. Our results provide genetic evidence that p27(Kip1) functions downstream of cyclin D1. ..
- Fuchs S, Herzog D, Sumara G, Büchmann Møller S, Civenni G, Wu X, et al. Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1. Cell Stem Cell. 2009;4:236-47 pubmed publisher..Thus, our data reveal distinct mechanisms for growth control of NCSCs from different developmental stages. ..
- Liu N, Bezprozvannaya S, Williams A, Qi X, Richardson J, Bassel Duby R, et al. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. 2008;22:3242-54 pubmed publisher....
- Salpeter S, Klochendler A, Weinberg Corem N, Porat S, Granot Z, Shapiro A, et al. Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic β-cells through glycolysis and calcium channels. Endocrinology. 2011;152:2589-98 pubmed publisher..These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and β-cell replication. ..
- Jena N, Deng M, Sicinska E, Sicinski P, Daley G. Critical role for cyclin D2 in BCR/ABL-induced proliferation of hematopoietic cells. Cancer Res. 2002;62:535-41 pubmed..These results establish that BCR/ABL promotes cell cycle progression by altering expression of cyclin D2 and that cyclin D2 induction plays a critical role in proliferation of hematopoietic cells by BCR/ABL. ..
- Rodriguez Puebla M, LaCava M, Miliani de Marval P, Jorcano J, Richie E, Conti C. Cyclin D2 overexpression in transgenic mice induces thymic and epidermal hyperplasia whereas cyclin D3 expression results only in epidermal hyperplasia. Am J Pathol. 2000;157:1039-50 pubmed..However, overexpression of each D-type cyclin produces a distinct phenotype in thymic epithelial cells. ..
- Darwich R, Li W, Yamak A, Komati H, Andelfinger G, Sun K, et al. KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. Hum Mol Genet. 2017;26:942-954 pubmed publisher..The data also suggest that, in human, KLF13 may be a genetic modifier of the Holt-Oram Syndrome gene TBX5...
- Zega K, Jovanovic V, Vitic Z, Niedzielska M, Knaapi L, Jukic M, et al. Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool. Front Mol Neurosci. 2017;10:372 pubmed publisher..Moreover our results suggest that a lack of functional Dusp16 could play a central role in the molecular mechanisms linking brain overgrowth and hydrocephalus...