Pocket proteins and cell cycle control

Cobrinik, David

doi:10.1038/sj.onc.1208619

Cited by 534 publications

(553 citation statements)

References 180 publications

(218 reference statements)

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“…The first substrate defined for CDK4/cyclin D1 complexes was the retinoblastoma tumor suppressor protein, RB Kato et al, 1993;Matsushime et al, 1992Matsushime et al, , 1994. In its active state, RB inhibits cell cycle progression through its ability to repress transactivation of genes required for DNA replication and G2/M progression (reviewed in Sherr and McCormick, 2002;Cam and Dynlacht, 2003;Cobrinik, 2005). Activated CDK4/cyclin D1 complexes initiate phosphorylation of RB in response to mitogens (Mittnacht, 1998;Harbour et al, 1999).…”

Section: Cyclin D1 and Cell Cycle Controlmentioning

confidence: 99%

Cyclin D1: polymorphism, aberrant splicing and cancer risk

et al. 2006

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The cyclin D1 proto-oncogene exercises powerful control over the mechanisms that regulate the mitotic cell cycle, and excessive cyclin D1 expression and/or activity is common in human cancers. Although somatic mutations of the cyclin D1 locus are rarely observed, mounting evidence demonstrates that a specific polymorphism of cyclin D1 (G/A870) and a protein product of a potentially related alternate splicing event (cyclin D1b) may influence cancer risk and outcome. Herein, we review the epidemiological and functional literatures that link these alterations of cyclin D1 to human tumor development and progression.

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Section: Cyclin D1 and Cell Cycle Controlmentioning

confidence: 99%

Cyclin D1: polymorphism, aberrant splicing and cancer risk

et al. 2006

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“…Taken together, these findings provide support for an important role of the pRB family members and the E2F transcription factors in the G 2 arrest. As the pRB family members interact with multiple binding partners and control a wide range of signaling pathways (Cobrinik, 2005), including cell cycle regulation, hypoxia signaling (Budde et al, 2005), and cancer development (Attwooll et al, 2004), the studies reported here were designed to determine whether E2F4 played a direct role in G 2 arrest following ionizing radiation (IR).…”

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confidence: 99%

E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma

et al. 2006

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The retinoblastoma (pRB) family proteins regulate the E2F transcription factors; their complexes regulate critical transitions through the cell cycle. The function of these pRB family/E2F complexes, which includes p130/ E2F4, in response to genotoxic agents, is not well understood. We investigated the role of E2F4 in the genotoxic stress response. Following radiation treatment, E2F4 colocalized with p130 in the nucleus during a radiation-induced stable G 2 -phase arrest. Arrested cells had significantly decreased expression of Cyclins A2 and B1 and decreased phosphorylation of mitotic protein monoclonal-2 (MPM-2) mitotic proteins. Small interference RNA (siRNA)-mediated knockdown of E2F4 sensitized cells to subsequent irradiation, resulting in enhanced cellular DNA damage and cell death, as determined by caspase activation and decreased clonogenic cell survival. Downstream E2F4 targets potentially involved in the progression from G 2 into M phase were identified by oligonucleotide microarray expression profiling. Chromatin immunoprecipitation localized E2F4 at promoter regions of the Bub3 and Pttg1 mitotic genes following irradiation, which were among the downregulated genes identified by the microarray. These data suggest that in response to radiation, E2F4 becomes active in the nucleus, enforces a stable G 2 arrest by target gene repression, and thus provides increased cell survival ability by minimizing propagation of cells that have irreparable DNA damage.

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“…pRb is maintained in a hypophosphorylated form during G0 but becomes increasingly phosphorylated during the G1 progression resulting from the action of mitogenic signals through cyclin-dependent kinases and this leads to the activation of E2F transcriptional activity. The details of these processes have been reviewed recently (Cobrinik, 2005). We will now consider the pathological effects of the large T-antigen of the three different human polyomaviruses on the function of pRb and its family members.…”

Section: The Retinoblastoma Family Of Proteinsmentioning

confidence: 99%

Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses

White

Khalili

2006

Oncogene

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The retinoblastoma gene product pRb and other members of the Rb family of pocket proteins have a central role in the regulation of cell cycle progression. Soon after its discovery, pRb was found to interact with the transforming oncoproteins of DNA tumor viruses and this led to rapid advances in our understanding of the mechanisms of viral transformation and cell cycle progression. DNA viruses of the polyomavirus family have small, circular, double-stranded DNA genomes contained within nonenveloped icosahedral capsids and are highly tumorigenic in experimental animals. At least three types of polyomavirus infect humans: JC virus (JCV), BK virus (BKV) and Simian Vacuolating virus-40. The early region of these viruses encodes the transforming proteins large T-antigen and small t-antigen, which are involved in viral replication and also promote transformation of cells in culture and oncogenesis in vivo. Binding of T-antigen to pRb promotes the activation of the E2F family of transcription factors, which induce the expression of cellular genes required for S phase. In the context of lytic infection, this cell cycle progression is necessary for viral replication because polyomaviruses rely on S phasespecific host factors for their DNA synthesis. In the context of cellular transformation and tumorigenesis, T-antigen/pRB interaction is an indispensable event.

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Pocket proteins and cell cycle control

Cited by 534 publications

References 180 publications

Cyclin D1: polymorphism, aberrant splicing and cancer risk

Cyclin D1: polymorphism, aberrant splicing and cancer risk

E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma

Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses

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