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Id helix-loop-helix proteins inhibit nucleoprotein complex formation by the TCF ETS-domain transcription factors

Lookup NU author(s): Dr Paula Yates

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Abstract

The Id subfamily of helix-loop-helix (HLH) proteins plays a fundamental role in the regulation of cellular proliferation and differentiation. Id proteins are thought to inhibit differentiation mainly through interaction with other ALH proteins and by blocking their DNA-binding activity. Members of the ternary complex factor (TCF) subfamily of ETS-domain proteins have key functions in regulating immediate-early gene expression in response to mitogenic stimulation. TCFs form DNA-bound complexes with the serum response factor (SRF) and are direct targets of MAP kinase (MAPK) signal transduction cascades, In this study we demonstrate functional interactions between Id proteins and TCFs, Ids bind to the ETS DNA-binding domain and disrupt the formation of DNA-bound complexes between TCFs and SRF on the c-fos serum response element (SRE), Inhibition occurs by disrupting protein-DNA interactions with the TCF component of this complex. lit vivo, the Id proteins cause do,vn-regulation of the transcriptional activity mediated by the TCFs and thereby block MAPK signalling to SREs, Therefore, our results demonstrate a novel facet of Id function in the coordination of mitogenic signalling and cell cycle entry.

Publication metadata

Author(s): Yates PR, Atherton GT, Deed RW, Norton JD, Sharrocks AD

Publication type: Article

Publication status: Published

Journal: EMBO Journal

Year: 1999

Volume: 18

Issue: 4

Pages: 968-976

Print publication date: 01/02/1999

ISSN (print): 0261-4189

ISSN (electronic): 1460-2075

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1093/emboj/18.4.968

DOI: 10.1093/emboj/18.4.968

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