Antibodies to E2F Transcription Factor Family

Introduction

About 20 years ago E2F transcription factors were found to be key regulators of cell cycle progression. Meanwhile a lot of diverse functions in controlling transcription, cell cycle and apoptosis have been described. E2F proteins are encoded by at least eight genes, E2F1 through E2F8.

The transcription factor E2F1 was identified as a DNA binding protein required for transcription of the adenovirus E2A promoter. The E2F binding site is also present in many growth-responsive and growth-promoting genes. E2F family members regulate these genes, in part, through their interaction with other cellular proteins. Included among these so-called nuclear pocket proteins are RB1, p107, and p130. E2F1, E2F2, and E2F3 are known targets of RB1, which inhibits transcription of target genes. Another member of the E2F family, also called DP-1, forms heterodimers with E2F1 which stimulate the DNA-binding and RB1-binding action of E2F1. E2F4, like E2F1, was shown to be able to form heterodimers with DP-1, and coexpression of E2F1 and E2F4 gave markedly higher levels of transcription from an E2-CAT reporter gene. However, it was shown that, unlike the other members of the E2F family, E2F4 interacts with p107 in vivo, an interaction which diminishes E2F4's trans-activating capacity. E2F1 and E2F4 proteins play a direct role in the regulation of early adipocyte differentiation. It was demonstrated that E2F family members bind in vitro and in vivo to the PPARG promoter. Depletion of E2F4 stimulated adipogenesis. It was concluded that E2F4 represses PPARG expression during terminal adipocyte differentiation. SMAD3 can mediate transcriptional repression of the growth-promoting gene MYC. A complex containing SMAD3, the transcription factors E2F4, E2F5, and DP1, and the corepressor p107 preexists in the cytoplasm. In response to TGF-beta, this complex moves into the nucleus and associates with SMAD4, recognizing a composite SMAD-E2F site on MYC for repression. Previously known as the ultimate recipients of CDK regulatory signals, E2F4/E2F5 and p107 act here as transducers of TGF-beta receptor signals upstream of CDK.

While many E2F proteins contain several evolutionarily conserved domains (a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain), the protein encoded by E2F6 is atypical because it lacks the transactivation and tumor suppressor protein association domains. It contains a modular suppression domain and is an inhibitor of E2F-dependent transcription. The protein is part of a multimeric protein complex that contains a histone methyltransferase and the transcription factors Mga and Max.

E2F7 can block the E2F-dependent activation of a subset of E2F target genes as well as mitigate cellular proliferation of mouse embryo fibroblasts.

E2F8 modulates the activity of other E2F proteins, such as E2F1, probably by competing or displacing activating E2Fs from promoter binding.

Antibody Tools for the Detection of Transcription Factors

Acris Antibodies offers a panel of antibodies for the detection of transcription factors E2F1 through E2F8. Antibodies can be used for immunohistochemistry, Western blotting or other immunological methods.

Fig.1: Formalin fixed paraffin embedded human tonsil stained with anti-E2F-1 antibody DM381

Fig.2: Western blot of Jurkat cell lysate using anti-E2F5 antibody P100920

Fig.3: Paraffin embedded mouse stomach stained with anti-E2F7 antibody ARP37583 (positive labelled epithelial cells of fundic gland are indicated with arrows).

Available Antibody Panel to E2F Transcription Factors

Anti- E2F1 (E2F-1, RBBP3, PBR3, RBAP1), E2F2 (E2F-2), E2F3 (E2F-3, KIAA0075), E2F4 (E2F-4), E2F5 (E2F-5), E2F6 (E2F-6), E2F7 (E2F-7), and E2F8 (E2F-8) antibody

Literature

DeGregori J, Johnson DG. Distinct and Overlapping Roles for E2F Family Members in Transcription, Proliferation and Apoptosis. Curr Mol Med. 2006 Nov;6(7):739-48

McClellan KA, Slack RS. Specific in vivo roles for E2Fs in differentiation and development. Cell Cycle. 2007 Sep;6(23):2917-27.

Attwooll C, Lazzerini Denchi E, Helin K. The E2F family: specific functions and overlapping interests. EMBO J. 2004 Dec 8;23(24):4709-16.

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