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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.

Pubmed ID: 11073990 RIS Download

Mesh terms: Acetyltransferases | Adenovirus E1A Proteins | Amino Acid Sequence | Cloning, Molecular | Gene Expression Regulation | Histone Acetyltransferases | Molecular Sequence Data | Muscle, Skeletal | MyoD Protein | Nuclear Proteins | Protein Binding | Repressor Proteins | Retinoblastoma Protein | Saccharomyces cerevisiae Proteins | Tissue Distribution | Trans-Activators | Transcriptional Activation | Two-Hybrid System Techniques

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Associated grants

  • Agency: NHLBI NIH HHS, Id: R01 HL61668
  • Agency: NHLBI NIH HHS, Id: R01 HL047567
  • Agency: NHLBI NIH HHS, Id: R01 HL47567
  • Agency: NHLBI NIH HHS, Id: K08 HL03671
  • Agency: NHLBI NIH HHS, Id: R01 HL061668

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