Post-Transcriptional Regulation of E2F Transcription Factors: Fine-Tuning DNA Repair, Cell Cycle Progression and Survival in Development & Disease

L. Dagnino,Randeep K. Singh,D. Judah

Published 2011 in Unknown venue

ABSTRACT

Cells are continually exposed to genotoxic stresses. Upon DNA damage, the cell activates a coordinated and complex series of responses (Levitt and Hickson, 2002). Multiple factors are implicated in each of these responses. Recently, it has become apparent that various transcription factors play important roles in cellular responses to genotoxic stress. In particular, E2F transcription factors are key for the activation of genes involved in these processes. E2F family comprises two subfamilies, termed E2F and DP, and includes orthologs expressed across many species, from plants to higher vertebrates (McClellan and Slack, 2007). In mammals, multiple E2F (E2F-1 through -8) and DP (DP-1 through -4) genes have been identified. E2F-1, -2 and -3 are associated with DNA synthesis and cell cycle progression, and function as heterodimers with a DP member (McClellan and Slack, 2007). E2F-4 and -5 also require association with a DP protein, but often function to halt cell cycle progression associated with terminal differentiation or reversible entry into quiescence (McClellan and Slack, 2007). E2F-1 through -5 can mediate transcriptional activation when found as ろfreeわ E2F/DP dimers, but can also act as transcriptional repressors if they are associated with a member of the retinoblastoma (pRb) family of proteins (Hallstrom and Nevins, 2009). In contrast, E2F-6 lacks both transcriptional activation and pRb-binding domains, and functions as a constitutive transcriptional repressor. The most divergent members of the E2F family are E2F-7 and -8, which bind neither DP nor pRb-family proteins, and also function as transcriptional repressors to mediate cell cycle arrest (Lammens et al., 2009). To regulate gene expression, E2F factors bind GC-rich elements on proximal promoters, which can conform to either a consensus 5’-TTTC[CG]CGC-3’ element, or to non-consensus sequences (Judah et al., 2010; Rabinovich et al., 2008). Considerable efforts have been directed to investigate whether different E2F proteins exhibit target selectivity. Genome-wide screens for E2F targets have revealed considerable overlap in the ability of individual E2F proteins to regulate their targets, although a few promoters activated by specific E2F forms have been identified (Cao et al., 2011).

PUBLICATION RECORD

  • Publication year

    2011

  • Venue

    Unknown venue

  • Publication date

    2011-11-07

  • Fields of study

    Biology, Medicine

  • Identifiers
  • External record

    Open on Semantic Scholar

  • Source metadata

    Semantic Scholar

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