EID-2, a novel member of the EID family of p300-binding proteins inhibits transactivation by MyoD.
Skeletal muscle differentiation has been shown to be dependent on the expression of Rb and p300. We recently cloned a novel inhibitor of muscle differentiation called EID-1, which interacted with both of these factors. In a database search for related molecules, we have cloned and characterized a new EID-1 family member, EID-2. This 28-kDa protein encodes a 236-amino-acid protein with significant similarity to EID-1 in its C-terminus. EID-2 displays developmentally regulated expression with high levels in adult heart and brain. Overexpression of EID-2 inhibits muscle-specific gene expression through inhibition of MyoD-dependent transcription. This inhibitory effect on gene expression can be explained by EID-2's ability to associate with and inhibit the acetyltransferase activity of p300. These data suggest that EID-1 and -2 represent a novel family of proteins that negatively regulate differentiation through a p300-dependent mechanism.
Ji
Aimin
A
Cardiovascular Research Laboratories, Department of Medicine, David Geffen School of Medicine at UCLA, MRL 3-645, 675 C.E. Young Dr, Los Angeles, CA 90095-1760, USA.
Dao
Diem
D
Chen
Jiexiao
J
MacLellan
W Robb
WR
D000123:Acetyltransferases / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D015870:Gene Expression; D051548:Histone Acetyltransferases; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D000199:Actins; D002352:Carrier Proteins; D018076:DNA, Complementary; C480629:EID-2 protein, mouse; C475090:EID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D047908:Intracellular Signaling Peptides and Proteins; D017570:MyoD Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D018995:Myosin Heavy Chains