A revised picture of the E2F transcriptional network and RB function

Stevaux, Olivier; Dyson, Nicholas J.

doi:10.1016/s0955-0674(02)00388-5

Cited by 391 publications

(342 citation statements)

References 51 publications

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“…The ultimate result of this interaction is that the cell cycle control, normally exerted by G1 cyclins-cyclindependent kinases (CDKs)-cyclin-dependent kinase inhibitors (CDKIs) through the regulation of pRb and pRb-like proteins phosphorylation, is bypassed. As a consequence of pRb displacement, E2F activates the transcription of a number of genes required to drive the cell into S phase and to induce DNA synthesis, including Cyclin A, Cyclin E and CDK2 (Stevaux and Dyson, 2002).…”

Section: Adenovirus Early-region 1amentioning

confidence: 99%

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Mileo²,

2006

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Section: Adenovirus Early-region 1amentioning

confidence: 99%

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Mileo²,

2006

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“…5,6 These proteins function as heterodimers with members of the DP family (DP1 and DP2), with the DNAbinding specificity being determined by the E2F subunit. The E2F family regulates overlapping sets of target genes and all contain related DNA binding and dimerisation domains.…”

Section: E2fs In Cell Cycle Controlmentioning

confidence: 99%

Life and death decisions by E2F-1

2003

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Deregulation of the transcription factor E2F-1 is a common event in most human cancers. Paradoxically, E2F-1 has been shown to have the ability to induce both cell cycle progression and programmed cell death, leading potentially to both tumour-promoting as well as tumour-suppressive effects. Although the pathway to cell cycle progression seems straightforward with a number of growth-promoting E2F target genes having been described, the pathways to apoptosis are less well defined and more complex. The discovery that E2F-1 'knockout' mice are highly tumour prone has caused a recent surge in the number of reports relating to programmed cell death. This review focuses on these recent findings, highlighting the way in which they have increased our understanding of E2F-1-induced cell death, as well as indicating the questions that remain. Insight gained as to the role of this intriguing molecule in cancer and its potential for targeted therapy will also be discussed.

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“…Repressor E2F/RB complexes are prevalent in G 0 /early G 1 phases, and they are disrupted in late G 1 , resulting primarily from the phosphorylation of RB proteins by cyclin D-CDK4/6 and cyclin E-CDK2 complexes. Late in G 1 , activator E2Fs turn on the transcription of genes required for entry into S phase and DNA synthesis (Trimarchi and Lees, 2002;DeGregori, 2002;Stevaux and Dyson, 2002). However, the ability of a particular E2F protein to either induce S phase, senescence, or some other outcome is dependent on the cellular context and on the particular groups of up-or down-regulated genes (Dimova and Dyson, 2005).…”

Section: Introductionmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

Marlowe

Fan

Chang

et al. 2008

MBoC

113

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Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr ؊/؊ fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, ␥H2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RBnegative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G 0 /G 1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. INTRODUCTIONMembers of the E2F family of transcription factors are critical regulators of the G 1 /S phase transition of the cell cycle, during which their transcriptional activity is generally controlled through interaction with retinoblastoma (RB) family proteins. In addition, E2F proteins have functions beyond the G 1 /S phase transition that impact cell proliferation in a variety of ways (Dimova and Dyson, 2005). The E2F family consists of six extensively characterized and three less wellstudied members. E2F1, -2, and -3a are potent activators of transcription, bind exclusively to RB-p105, and are cyclically expressed during the cell cycle. E2F3b and -4, which can interact with RB-p107 and -p130, and E2F5, which binds only to p130, are poor transcriptional activators, and they function mainly as repressors through their recruitment of RB proteins to E2F-regulated promoters (Dyson, 1998;Nevins, 1998;DeGregori and Johnson, 2006). In general, the E2Fs with transactivator activity promote cell cycle progression, whereas the E2Fs with transrepressor activity function in cell cycle exit and differentiation (Dimova and Dyson, 2005). E2F6-8 are distinct from the other E2F members, lacking the transactivation and RB-binding domains, and they repress transcription in an RB-independent manner (Frolov and Dyson, 2004;DeGregori and Johnson, 2006).The best-characterized function of E2F ...

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A revised picture of the E2F transcriptional network and RB function

Cited by 391 publications

References 51 publications

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

Life and death decisions by E2F-1

The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

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