A novel Rb- and p300-binding protein inhibits transactivation by MyoD.
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 G(1) 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.
MacLellan
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WR
Cardiovascular Research Laboratories, Department of Medicine, UCLA School of Medicine, Los Angeles, California 90095, USA. rmaclellan@mednet.ucla.edu
Xiao
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G
Abdellatif
M
M
Schneider
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MD
D000123:Acetyltransferases / Q000037:antagonists & inhibitors; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
D017500:Adenovirus E1A Proteins; D018797:Cell Cycle Proteins; C416925:EID1 protein, human; D017570:MyoD Protein; D009687:Nuclear Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D051548:Histone Acetyltransferases