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RFP represses transcriptional activation by bHLH transcription factors

Oncogene volume 24, pages 6729–6736 (2005)Cite this article

Abstract

Basic helix–loop–helix (bHLH) transcription factors play a pivotal role in the regulation of tumorigenesis, and also in a wide range of other developmental processes in diverse species from yeast to humans. Here we demonstrate for the first time that Ret finger protein (RFP), a member of the TRIM family of proteins initially identified as a recombined transforming gene from a human lymphoma, is a novel interaction partner for four different bHLH proteins (SCL, E47, MyoD and mASH-1), but does not interact with GATA-1 or PU.1. Interaction with SCL required the B-box and first coiled-coil region of RFP together with the bHLH domain of SCL. RFP was able to repress transcriptional activation by E47, MyoD and mASH-1, but not by members of several other transcription factor families. Transcriptional repression by RFP was trichostatin A sensitive and did not involve an Id-like mechanism or ubiquitination with subsequent degradation of bHLH proteins. Instead, our results suggest that bHLH transcription factors are regulated by a previously undescribed interaction with RFP, which functions to recruit HDAC and/or Polycomb proteins and thus repress target genes of bHLH proteins. These results reveal an unexpected link between the bHLH and TRIM protein families.

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Acknowledgements

We are grateful to Dr Larry Etkin for the provision of reagents and Dr Bertie Gottgens for constructive comments and advice. This work was supported by the Leukemia Research Fund and the Wellcome Trust. AB was supported by the Raymond and Beverly Sackler Foundation.

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Author notes

  1. Adrian Bloor and Ekaterina Kotsopoulou: These two authors contributed equally to this work

Authors and Affiliations

  1. Department of Haematology, Cambridge Institute for Medical Research, Cambridge University, Hills Road, Cambridge, CB2 2XY, UK

    Adrian Bloor, Ekaterina Kotsopoulou & Anthony Green

  2. Department of Genetics, Cambridge University, Cambridge, CB2 3EH, UK

    Penny Hayward

  3. Lorantis Ltd, Cambridge, CB4 0WG, UK

    Brian Champion

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  1. Adrian Bloor
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  2. Ekaterina Kotsopoulou
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Correspondence to Anthony Green.

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Bloor, A., Kotsopoulou, E., Hayward, P. et al. RFP represses transcriptional activation by bHLH transcription factors. Oncogene 24, 6729–6736 (2005). https://doi.org/10.1038/sj.onc.1208828

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