Repression of E2F-4 Mediated Transcription and Growth by Hypophosphorylated pRb2/p130 in Human Prostate Cancer Cells
type: CreativeWork
description: A fundamental property of tumor cells is the ability to proliferate in an unscheduled manner, circumventing the cues which would otherwise prevent entry into, and completion of, the cell cycle (Malumbres, Barbacid 2001). The retinoblastoma protein (pRb), and its homologues pRb2/p130 and p107, comprise a gene family which is central in maintaining appropriate cell proliferation and differentiation. The RB proteins bind to and modulate the activity of E2F transcription factors, by way of a unique binding motif termed the pocket domain; as such, RB family genes are often referred to as pocket proteins. E2F -1, -2, and -3 are considered transcriptional activators and have been shown mainly to bind pRB, whereas E2F -4 and -5 are considered transcriptional repressors, and primarily bind p107 and pRb2/p130 (Classon, Dyson 2001, Cobrinik 2005). The commonly accepted model of pRb2/p130 function is that, during quiescence, pRb2/p130, bound to E2F-4 and -5, is an active repressor of E2F responsive S-phase genes, which includes p107 and a number of cyclins (Figure 1). Upon entry into G1, the many phosphoacceptor sites of pRb2/p130 are progressively phosphorylated, disrupting the repressor complex, and allowing the transcription of downstream targets. pRb2/p130 is acted upon by the same early and late G1 kinases which phosphorylate pRb and p107, namely cyclin dependant kinases (cdk) 4 and 6, which partner with cyclin D, and later by cdk2, which requires cyclin E or A. pRb phosphorylation is required to prevent its inhibition of E2F transcription, which would otherwise halt cell cycle progression. E2F transcriptional activity permits the cell to traverse the G1/S restriction point by, among other effects, promoting cdk2 activity, which maintains pocket protein inactivation and E2F activity in a positive feedback fashion. By interacting with different sets of E2F proteins to repress transcription, pRb and pRb2/p130 act in a parallel manner to restrict cell proliferation (Classon, …
abstract: A fundamental property of tumor cells is the ability to proliferate in an unscheduled manner, circumventing the cues which would otherwise prevent entry into, and completion of, the cell cycle (Malumbres, Barbacid 2001). The retinoblastoma protein (pRb), and its homologues pRb2/p130 and p107, comprise a gene family which is central in maintaining appropriate cell proliferation and differentiation. The RB proteins bind to and modulate the activity of E2F transcription factors, by way of a unique binding motif termed the pocket domain; as such, RB family genes are often referred to as pocket proteins. E2F -1, -2, and -3 are considered transcriptional activators and have been shown mainly to bind pRB, whereas E2F -4 and -5 are considered transcriptional repressors, and primarily bind p107 and pRb2/p130 (Classon, Dyson 2001, Cobrinik 2005). The commonly accepted model of pRb2/p130 function is that, during quiescence, pRb2/p130, bound to E2F-4 and -5, is an active repressor of E2F responsive S-phase genes, which includes p107 and a number of cyclins (Figure 1). Upon entry into G1, the many phosphoacceptor sites of pRb2/p130 are progressively phosphorylated, disrupting the repressor complex, and allowing the transcription of downstream targets. pRb2/p130 is acted upon by the same early and late G1 kinases which phosphorylate pRb and p107, namely cyclin dependant kinases (cdk) 4 and 6, which partner with cyclin D, and later by cdk2, which requires cyclin E or A. pRb phosphorylation is required to prevent its inhibition of E2F transcription, which would otherwise halt cell cycle progression. E2F transcriptional activity permits the cell to traverse the G1/S restriction point by, among other effects, promoting cdk2 activity, which maintains pocket protein inactivation and E2F activity in a positive feedback fashion. By interacting with different sets of E2F proteins to repress transcription, pRb and pRb2/p130 act in a parallel manner to restrict cell proliferation (Classon, …
author: Tutton, Stephen Paul
language: eng
keywords: Biology
license: http://rightsstatements.org/vocab/InC/1.0/
date published: 2011
date modified: 2026-07-27T21:20:27Z
provider: Temple University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Temple University. Libraries

PropertyValue
property ID: Handle
value: http://hdl.handle.net/20.500.12613/3636