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Molecular and Cellular Biology, December 2000, p. 8903-8915, Vol. 20, No. 23
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Novel Rb- and p300-Binding Protein Inhibits Transactivation by MyoD

W. Robb MacLellan,1,* G. Xiao,1 M. Abdellatif,2 and Michael D. Schneider2,3,4

Cardiovascular Research Laboratories, Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095,1 and Departments of Medicine,2 Molecular and Cellular Biology,3 and Molecular Physiology and Biophysics,4 Baylor College of Medicine, Houston, Texas 77401

Received 8 May 2000/Returned for modification 10 July 2000/Accepted 14 September 2000

The retinoblastoma protein (Rb) regulates both the cell cycle and tissue-specific transcription, by modulating the activity of factors that associate with its A-B and C pockets. In skeletal muscle, Rb has been reported to regulate irreversible cell cycle exit and muscle-specific transcription. To identify factors interacting with Rb in muscle cells, we utilized the yeast two-hybrid system, using the A-B and C pockets of Rb as bait. A novel protein we have designated E1A-like inhibitor of differentiation 1 (EID-1), was the predominant Rb-binding clone isolated. It is preferentially expressed in adult cardiac and skeletal muscle and encodes a 187-amino-acid protein, with a classic Rb-binding motif (LXCXE) in its C terminus. Overexpression of EID-1 in skeletal muscle inhibited tissue-specific transcription. Repression of skeletal muscle-restricted genes was mediated by a block to transactivation by MyoD independent of G1 exit and, surprisingly, was potentiated by a mutation that prevents EID-1 binding to Rb. Inhibition of MyoD may be explained by EID-1's ability to bind and inhibit p300's histone acetylase activity, an essential MyoD coactivator. Thus, EID-1 binds both Rb and p300 and is a novel repressor of MyoD function.

* Corresponding author. Mailing address: Cardiovascular Research Laboratories, UCLA School of Medicine, Macdonald Research Laboratories Building, 675 Circle Dr. South, Rm. 3645, Los Angeles, CA 90095-1760. Phone: (310) 825-2556. Fax: (310) 206-5777. E-mail: rmaclellan{at}mednet.ucla.edu.

Molecular and Cellular Biology, December 2000, p. 8903-8915, Vol. 20, No. 23
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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