The activities of cyclin D1 that drive tumorigenesis.
The proto-oncogene cyclin D1 has been implicated in the genesis of a large proportion of human tumors from diverse histological origins. It has long been assumed that the action of cyclin D1, as an activator of cdk4 and cdk6 and leading to progression through the G1 phase of the cell cycle, underlies its pathological activity. But, more recently, analyses of the patterns of gene expression in human cancer have revealed a previously unappreciated mechanism of action for cyclin D1, suggesting that both cdk-dependent and cdk-independent activities might contribute to tumorigenesis. The development of therapeutics designed to target the aberrant activity of cyclin D1 in human cancers will rely upon an intimate molecular understanding of these distinct mechanisms of actions and their relative importance. Here, we describe the known functions of the cyclin D1 oncogene and delineate the evidence that cdk-independent actions are important for cyclin D1-mediated oncogenesis.
Ewen
Mark E
ME
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. mark_ewen@dfci.harvard.edu
Lamb
Justin
J
D000818:Animals; D018929:Cell Culture Techniques; D002453:Cell Cycle; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism / Q000502:physiology*; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; C495900:CDK4 protein, human; C495911:CDK6 protein, human; C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases