Cyclin D1, cancer progression, and opportunities in cancer treatment.
Mammalian cells encode three D cyclins (D1, D2, and D3) that coordinately function as allosteric regulators of cyclin-dependent kinase 4 (CDK4) and CDK6 to regulate cell cycle transition from G1 to S phase. Cyclin expression, accumulation, and degradation, as well as assembly and activation of CDK4/CDK6 are governed by growth factor stimulation. Cyclin D1 is more frequently dysregulated than cyclin D2 or D3 in human cancers, and as such, it has been more extensively characterized. Overexpression of cyclin D1 results in dysregulated CDK activity, rapid cell growth under conditions of restricted mitogenic signaling, bypass of key cellular checkpoints, and ultimately, neoplastic growth. This review discusses cyclin D1 transcriptional, translational, and post-translational regulations and its biological function with a particular focus on the mechanisms that result in its dysregulation in human cancers.
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, Charleston, SC, 29425, USA.
Shuo
S
Qie
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, Charleston, SC, 29425, USA. diehl@musc.edu.
J Alan
JA
Diehl
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D015398:Signal Transduction; D014158:Transcription, Genetic; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D051176:beta Catenin; D019938:Cyclin D1; D058539:Phosphatidylinositol 3-Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
CDK4/CDK6; Cancer; Cyclin D1; Post-translational regulation; Proteasome
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