Genomes and Genes
Gene Symbol: Ccnd1
Description: cyclin D1
Alias: AI327039, CycD1, Cyl-1, PRAD1, bcl-1, cD1, G1/S-specific cyclin-D1
- Voronina V, Takemaru K, Treuting P, Love D, Grubb B, Hajjar A, et al. Inactivation of Chibby affects function of motile airway cilia. J Cell Biol. 2009;185:225-33 pubmed publisher..As the phenotypes of Cby(-/-) mice bear striking similarities to primary ciliary dyskinesia, Cby(-/-) mice may prove to be a useful model for this condition. ..
- Sigulinsky C, Green E, Clark A, Levine E. Vsx2/Chx10 ensures the correct timing and magnitude of Hedgehog signaling in the mouse retina. Dev Biol. 2008;317:560-75 pubmed publisher..Our results suggest that reduced Hh signaling contributes to the reduced level of RPC proliferation in the orJ retina, thereby revealing a role for Vsx2 in mediating mitogen signaling. ..
- Mill P, Mo R, Hu M, Dagnino L, Rosenblum N, Hui C. Shh controls epithelial proliferation via independent pathways that converge on N-Myc. Dev Cell. 2005;9:293-303 pubmed..These findings demonstrate that Shh signaling controls the rapid and patterned expansion of epithelial progenitors through convergent Gli-mediated regulation. ..
- 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)...
- Fu M, Rao M, Bouras T, Wang C, Wu K, Zhang X, et al. Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment. J Biol Chem. 2005;280:16934-41 pubmed
- Lange C, Huttner W, Calegari F. Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors. Cell Stem Cell. 2009;5:320-31 pubmed publisher..Thus, G1 lengthening is necessary and sufficient to switch neural progenitors to neurogenesis, and overexpression of cdk4/cyclinD1 can be used to increase progenitor expansion and, perhaps, cortical surface area. ..
- Mullany L, Hanse E, Romano A, Blomquist C, Mason J, Delvoux B, et al. Cyclin D1 regulates hepatic estrogen and androgen metabolism. Am J Physiol Gastrointest Liver Physiol. 2010;298:G884-95 pubmed publisher..Furthermore, these results suggest that increased cyclin D1 expression, which occurs in liver regeneration and liver diseases, may contribute to the feminization seen in these settings. ..
- Lee N, Sowa H, Hinoi E, Ferron M, Ahn J, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456-69 pubmed..By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism. ..
- Hitomi M, Yang K, Stacey A, Stacey D. Phosphorylation of cyclin D1 regulated by ATM or ATR controls cell cycle progression. Mol Cell Biol. 2008;28:5478-93 pubmed publisher..These results indicate that checkpoint kinases play a critical role in regulating cell cycle progression in normal and stressed cells by directing the phosphorylation of cyclin D1. ..
- Choi Y, Li X, Hydbring P, Sanda T, Stefano J, Christie A, et al. The requirement for cyclin D function in tumor maintenance. Cancer Cell. 2012;22:438-51 pubmed publisher..Inhibition of cyclin D-kinase activity represents a highly-selective anticancer strategy that specifically targets cancer cells without significantly affecting normal tissues. ..
- 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. ..
- Lin D, Barbash O, Kumar K, Weber J, Harper J, Klein Szanto A, et al. Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell. 2006;24:355-66 pubmed..We conclude that SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1. ..
- Casimiro M, Crosariol M, Loro E, Ertel A, Yu Z, Dampier W, et al. ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice. J Clin Invest. 2012;122:833-43 pubmed publisher..b>CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in ..
- Cain S, Martinez G, Kokkinos M, Turner K, Richardson R, Abud H, et al. Differential requirement for beta-catenin in epithelial and fiber cells during lens development. Dev Biol. 2008;321:420-33 pubmed publisher..These data indicate that beta-catenin plays distinct functions during lens fiber differentiation and is involved in both Wnt signaling and adhesion-related mechanisms that regulate lens epithelium and early fiber differentiation. ..
- Kozar K, Sicinski P. Cell cycle progression without cyclin D-CDK4 and cyclin D-CDK6 complexes. Cell Cycle. 2005;4:388-91 pubmed..Intriguingly, several compartments can develop in the absence of cyclin D-CDK4/6 activity, revealing that these cells can proliferate in a cyclin D-independent fashion. ..
- Fu X, Sun H, Klein W, Mu X. Beta-catenin is essential for lamination but not neurogenesis in mouse retinal development. Dev Biol. 2006;299:424-37 pubmed..The results further imply that retinal lamination and retinal cell differentiation are genetically separable processes. ..
- Pogoriler J, Millen K, Utset M, Du W. Loss of cyclin D1 impairs cerebellar development and suppresses medulloblastoma formation. Development. 2006;133:3929-37 pubmed..Coinciding with the period of cyclin D1-only expression, Ccnd1(-/-) mice showed reduced proliferation of GNPs and impaired growth of the cerebellum...
- Gladden A, Woolery R, Aggarwal P, Wasik M, Diehl J. Expression of constitutively nuclear cyclin D1 in murine lymphocytes induces B-cell lymphoma. Oncogene. 2006;25:998-1007 pubmed..Our results describe a cyclin D1-driven model of B-cell lymphomagenesis and provide evidence that nuclear-retention of cyclin D1 is oncogenic in vivo. ..
- Adolphe C, Hetherington R, Ellis T, Wainwright B. Patched1 functions as a gatekeeper by promoting cell cycle progression. Cancer Res. 2006;66:2081-8 pubmed..quot; In addition, we note the high frequency and rapid onset of tumors in this mouse model makes it an ideal system for testing therapeutic strategies, such as Patched pathway inhibitors. ..
- Cai Z, Feng G, Zhang X. Temporal requirement of the protein tyrosine phosphatase Shp2 in establishing the neuronal fate in early retinal development. J Neurosci. 2010;30:4110-9 pubmed publisher..Together, these results demonstrate that Shp2 mediates FGF-Ras signaling to control retinal progenitor cell fate. ..
- 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. ..
- Yu Z, Wang C, Wang M, Li Z, Casimiro M, Liu M, et al. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol. 2008;182:509-17 pubmed publisher..In turn, miR-17/20 limits the proliferative function of cyclin D1, thus linking expression of a specific miRNA cluster to the regulation of oncogenesis. ..
- Li Z, Wang C, Jiao X, Lu Y, Fu M, Quong A, et al. Cyclin D1 regulates cellular migration through the inhibition of thrombospondin 1 and ROCK signaling. Mol Cell Biol. 2006;26:4240-56 pubmed..Cyclin D1 promotes cellular motility through inhibiting ROCK signaling and repressing the metastasis suppressor TSP-1. ..
- 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. ..
- Nelsen C, Kuriyama R, Hirsch B, Negron V, Lingle W, Goggin M, et al. Short term cyclin D1 overexpression induces centrosome amplification, mitotic spindle abnormalities, and aneuploidy. J Biol Chem. 2005;280:768-76 pubmed..These results indicate that cyclin D1 can induce deregulation of the mitotic apparatus and aneuploidy, effects that could contribute to the role of this oncogene in malignancy. ..
- 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..The finding that postnatal upregulation of a cell-cycle gene in GATA4 haplo-insufficient hearts may be protective opens new avenues for maintaining or restoring cardiac function in GATA4-dependent cardiac disease. ..
- Labalette C, Nouet Y, Sobczak Thepot J, Armengol C, Levillayer F, Gendron M, et al. The LIM-only protein FHL2 regulates cyclin D1 expression and cell proliferation. J Biol Chem. 2008;283:15201-8 pubmed publisher..Our study illustrates that FHL2 can act on different aspects of the cell cycle program to finely regulate cell proliferation. ..
- Murtaugh L, Law A, Dor Y, Melton D. Beta-catenin is essential for pancreatic acinar but not islet development. Development. 2005;132:4663-74 pubmed..Thus, our data are consistent with a crucial role for canonical Wnt signals in acinar lineage specification and differentiation. ..
- Chen Z, Duan R, Zhu Y, Folkesson R, Albanese C, Winblad B, et al. Increased cyclin E expression may obviate the role of cyclin D1 during brain development in cyclin D1 knockout mice. J Neurochem. 2005;92:1281-4 pubmed..The data indicate that enhanced cyclin E protein expression in cyclin D1 KO mice may obviate the role of cyclin D1 and contribute to the normal brain development of cyclin D1 KO mice. ..
- Manuel M, Martynoga B, Yu T, West J, Mason J, Price D. The transcription factor Foxg1 regulates the competence of telencephalic cells to adopt subpallial fates in mice. Development. 2010;137:487-97 pubmed publisher..These findings indicate that, in addition to regulating the production of ventralising signals, Foxg1 acts cell-autonomously in the telencephalon to ensure that cells develop the competence to adopt ventral identities. ..
- Tang M, Villaescusa J, Luo S, Guitarte C, Lei S, Miyamoto Y, et al. Interactions of Wnt/beta-catenin signaling and sonic hedgehog regulate the neurogenesis of ventral midbrain dopamine neurons. J Neurosci. 2010;30:9280-91 pubmed publisher..Persistent activation of beta-catenin in early progenitors perturbs their cell cycle progression and antagonizes Shh expression, whereas activation of beta-catenin in midline progenitors promotes the generation of dopamine neurons. ..
- 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..of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null (Ccnd1(-/-)) retinas...
- Landis M, Pawlyk B, Li T, Sicinski P, Hinds P. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell. 2006;9:13-22 pubmed..These results demonstrate a differential requirement for cyclin D1-CDK4/6 kinase activity in development versus tumorigenesis and strongly support cyclin D1-dependent kinase activity as a specific therapeutic target in breast cancer. ..
- Fotaki V, Smith R, Pratt T, Price D. Foxg1 is required to limit the formation of ciliary margin tissue and Wnt/?-catenin signalling in the developing nasal retina of the mouse. Dev Biol. 2013;380:299-313 pubmed publisher..Our results reveal a new role of Foxg1 in limiting CM development in the nasal peripheral retina and add a new molecular player in the developmental network involved in CM specification. ..
- Das G, Choi Y, Sicinski P, Levine E. Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells. Neural Dev. 2009;4:15 pubmed publisher..cell cycle regulator cyclin D1 is expressed in RPCs, and mice with a targeted null allele at the cyclin D1 locus (Ccnd1-/-) have microphthalmia and hypocellular retinas, the latter phenotype attributed to reduced RPC proliferation and ..
- Li Z, Wang C, Jiao X, Katiyar S, Casimiro M, Prendergast G, et al. Alternate cyclin D1 mRNA splicing modulates p27KIP1 binding and cell migration. J Biol Chem. 2008;283:7007-15 pubmed publisher..Our findings argue that alternate splicing is an important determinant of the function of cyclin D1 in cellular migration. ..
- Donovan S, Schweers B, Martins R, Johnson D, Dyer M. Compensation by tumor suppressor genes during retinal development in mice and humans. BMC Biol. 2006;4:14 pubmed..Together, these data suggest a model that explains why humans are susceptible to retinoblastoma following RB1 loss, but mice require both Rb and p107 gene inactivation. ..
- Fu M, Wang C, Rao M, Wu X, Bouras T, Zhang X, et al. Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism. J Biol Chem. 2005;280:29728-42 pubmed..Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300. ..
- Bienvenu F, Barré B, Giraud S, Avril S, Coqueret O. Transcriptional regulation by a DNA-associated form of cyclin D1. Mol Biol Cell. 2005;16:1850-8 pubmed..Altogether, these results suggest that the transcriptional activities of cyclin D1 might play an important role in the regulation of cell-cycle regulatory genes and that these functions are probably involved in cell transformation. ..
- Carthon B, Neumann C, Das M, Pawlyk B, Li T, Geng Y, et al. Genetic replacement of cyclin D1 function in mouse development by cyclin D2. Mol Cell Biol. 2005;25:1081-8 pubmed..We reason that the acquisition of multiple D cyclins may allow mammalian cells to drive optimal proliferation of a diverse array of cell types. ..
- Clark A, Yun S, Veien E, Wu Y, Chow R, Dorsky R, et al. Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the vertebrate retina. Brain Res. 2008;1192:99-113 pubmed
- Nakajima K, Inagawa M, Uchida C, Okada K, Tane S, Kojima M, et al. Coordinated regulation of differentiation and proliferation of embryonic cardiomyocytes by a jumonji (Jarid2)-cyclin D1 pathway. Development. 2011;138:1771-82 pubmed publisher..Thus, a Jmj-cyclin D1 pathway coordinately regulates proliferation and differentiation of cardiomyocytes. ..
- Pontano L, Aggarwal P, Barbash O, Brown E, Bassing C, Diehl J. Genotoxic stress-induced cyclin D1 phosphorylation and proteolysis are required for genomic stability. Mol Cell Biol. 2008;28:7245-58 pubmed publisher..These data suggest that failure to degrade cyclin D1 compromises the intra-S-phase checkpoint and suggest that cyclin D1 degradation is a vital cellular response necessary to prevent genomic instability following genotoxic insult. ..
- Yu H, Liu B, Costantini F, Hsu W. Impaired neural development caused by inducible expression of Axin in transgenic mice. Mech Dev. 2007;124:146-56 pubmed..Our data support the conclusion that the development of embryonic neural axis is highly sensitive to the level of Wnt signaling. ..
- Georgopoulou N, Hurel C, Politis P, Gaitanou M, Matsas R, Thomaidou D. BM88 is a dual function molecule inducing cell cycle exit and neuronal differentiation of neuroblastoma cells via cyclin D1 down-regulation and retinoblastoma protein hypophosphorylation. J Biol Chem. 2006;281:33606-20 pubmed
- Das G, Clark A, Levine E. Cyclin D1 inactivation extends proliferation and alters histogenesis in the postnatal mouse retina. Dev Dyn. 2012;241:941-52 pubmed publisher..The initial production of Müller glia and bipolar cells was enhanced in Cyclin D1 knockout (Ccnd1(-/-) ) retinas...
- Yip D, Corcoran C, Alvarez Saavedra M, Demaria A, Rennick S, Mears A, et al. Snf2l regulates Foxg1-dependent progenitor cell expansion in the developing brain. Dev Cell. 2012;22:871-8 pubmed publisher..We demonstrate that Snf2l binds to the Foxg1 locus at midneurogenesis and that the phenotype is rescued by reducing Foxg1 dosage, thus revealing that Snf2l and Foxg1 function antagonistically to regulate brain size. ..
- Datta N, Pettway G, Chen C, Koh A, McCauley L. Cyclin D1 as a target for the proliferative effects of PTH and PTHrP in early osteoblastic cells. J Bone Miner Res. 2007;22:951-64 pubmed..These data indicate that PTH and PTHrP induce cyclin D1 expression in early osteoblastic cells and their action is developmental stage specific. ..
- Laine H, Sulg M, Kirjavainen A, Pirvola U. Cell cycle regulation in the inner ear sensory epithelia: role of cyclin D1 and cyclin-dependent kinase inhibitors. Dev Biol. 2010;337:134-46 pubmed publisher..Thus, cyclin D1 critically contributes to the proliferative plasticity of supporting cells. These data suggest that targeted cyclin D1 induction in supporting cells might be an avenue for proliferative regeneration in the inner ear. ..
- Aggarwal P, Lessie M, Lin D, Pontano L, Gladden A, Nuskey B, et al. Nuclear accumulation of cyclin D1 during S phase inhibits Cul4-dependent Cdt1 proteolysis and triggers p53-dependent DNA rereplication. Genes Dev. 2007;21:2908-22 pubmed..Collectively, the data presented reveal mechanistic insights into how uncoupling of critical cell cycle regulatory events will perturb DNA replication fidelity, thereby contributing to neoplastic transformation. ..
- 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. ..
- Wang Y, Dakubo G, Thurig S, Mazerolle C, Wallace V. Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development. 2005;132:5103-13 pubmed
- Yu H, Jerchow B, Sheu T, Liu B, Costantini F, Puzas J, et al. The role of Axin2 in calvarial morphogenesis and craniosynostosis. Development. 2005;132:1995-2005 pubmed..The craniofacial anomalies caused by the Axin2 mutation are mediated through activation of beta-catenin signaling, suggesting a novel role for the Wnt pathway in skull morphogenesis. ..
- Alt J, Gladden A, Diehl J. p21(Cip1) Promotes cyclin D1 nuclear accumulation via direct inhibition of nuclear export. J Biol Chem. 2002;277:8517-23 pubmed..The ability of p21(Cip1) to inhibit cyclin D1 nuclear export correlates with its ability to bind to Thr-286-phosphorylated cyclin D1 and thereby prevents cyclin D1.CRM1 association. ..
- Lahti J, Li H, Kidd V. Elimination of cyclin D1 in vertebrate cells leads to an altered cell cycle phenotype, which is rescued by overexpression of murine cyclins D1, D2, or D3 but not by a mutant cyclin D1. J Biol Chem. 1997;272:10859-69 pubmed..Thus, there may be distinct differences in cyclin D1 complexes and/or its target(s) in proliferating and apoptotic DT40 lymphoma B-cells. ..
- Hulit J, Wang C, Li Z, Albanese C, Rao M, Di Vizio D, et al. Cyclin D1 genetic heterozygosity regulates colonic epithelial cell differentiation and tumor number in ApcMin mice. Mol Cell Biol. 2004;24:7598-611 pubmed..The protection of mice, genetically predisposed to intestinal tumorigenesis, through cyclin D1 heterozygosity suggests that modalities that reduce cyclin D1 abundance could provide chemoprotection. ..
- Akiyama H, Lyons J, Mori Akiyama Y, Yang X, Zhang R, Zhang Z, et al. Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev. 2004;18:1072-87 pubmed..Our results strongly suggest that chondrogenesis is controlled by interactions between Sox9 and the Wnt/beta-catenin signaling pathway. ..
- Sumrejkanchanakij P, Tamamori Adachi M, Matsunaga Y, Eto K, Ikeda M. Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons. Oncogene. 2003;22:8723-30 pubmed..These results indicate that nuclear accumulation of cyclin D1 is inhibited in postmitotic neurons and suggest a role of its subcellular localization in neuronal death and survival. ..
- Muraoka R, Lenferink A, Law B, Hamilton E, Brantley D, Roebuck L, et al. ErbB2/Neu-induced, cyclin D1-dependent transformation is accelerated in p27-haploinsufficient mammary epithelial cells but impaired in p27-null cells. Mol Cell Biol. 2002;22:2204-19 pubmed..These results suggest that p27(+/-) mammary epithelium may be more susceptible to oncogene-induced tumorigenesis, whereas p27-null glands, due to severely impaired cyclin D1/Cdk4 function, are more resistant to transformation. ..