Role of E2F in cell cycle control and cancer.
E2F transcription factors regulate the expression of a number of genes important in cell proliferation, particularly those involved in progression through G1 and into the S-phase of the cell cycle. The activity of E2F factors is regulated through association with the retinoblastoma tumor suppressor protein (Rb) and the other pocket proteins, p107 and p130. Binding of Rb, p107 or p130 converts E2F factors from transcriptional activators to transcriptional repressors. The interplay among G1 cyclins (D-type cyclins and cyclin E), cyclin-dependent kinases (cdk4, 6, and 2), cdk inhibitors, and protein phosphatases determines the phosphorylation state of the pocket proteins which in turn regulates the ability of the pocket proteins to complex with E2F. E2F activity is further regulated through direct interactions with other factors, such cyclin A, Sp1, p53 and the ubiquitin-proteasome pathway. Deregulated expression of E2F family member genes has been shown to induce both inappropriate S phase entry and apoptosis. An important role for E2F in the development of cancer is suggested by the finding that in most human neoplasias, genetic or epigenetic alterations occur that ultimately result in the deregulation of E2F-dependent transcription. This review will highlight recent findings on the specific roles of the individual E2F species in regulating transcription, proliferation and apoptosis, and discuss the growing link between E2F and cancer.
Johnson
D G
DG
The University of Texas M. D. Anderson Cancer Center, Science Park-Research, Division, Department of Carcinogenesis, P.O. Box 389, Smithville, TX 78957, USA. sa83202@odin.mdacc.tmc.edu
Schneider-Broussard
R
R
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein; D014157:Transcription Factors / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors