Role of E2F in cell cycle control and cancer

Frontiers in Bioscience : a Journal and Virtual Library
D G Johnson, R Schneider-Broussard

Abstract

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 transcrip...Continue Reading

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