EID3 is a novel EID family member and an inhibitor of CBP-dependent co-activation.

EID1 (E1A-like inhibitor of differentiation 1) functions as an inhibitor of nuclear receptor-dependent gene transcription by directly binding to co-regulators. Alternative targets include the co-repressor small heterodimer partner (SHP, NR0B2) and the co-activators CBP/p300, indicating that EID1 utilizes different inhibitory strategies. Recently, EID2 was characterized as an inhibitor of muscle ...
differentiation and as an antagonist of both CBP/p300 and HDACs. Here, we describe a third family member designated EID3 that is highly expressed in testis and shows homology to a region of EID1 implicated in binding to CBP/p300. We demonstrate that EID3 acts as a potent inhibitor of nuclear receptor transcriptional activity by a mechanism that is independent of direct interactions with nuclear receptors, including SHP. Furthermore, EID3 directly binds to and blocks the SRC-1 interacting domain of CBP, which has been implicated to act as the interaction surface for nuclear receptor co-activators. Consistent with this idea, EID3 prevents recruitment of CBP to a natural nuclear receptor-regulated promoter. Our study suggests that EID-family members EID3 and EID1 act as inhibitors of CBP/p300-dependent transcription in a tissue-specific manner.
Mesh Terms:
Adenovirus E1A Proteins, Animals, CREB-Binding Protein, Carrier Proteins, Cell Line, Cloning, Molecular, Gene Expression Regulation, Humans, Male, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Protein Structure, Tertiary, Proteins, Receptors, Cytoplasmic and Nuclear, Repressor Proteins, Testis, Trans-Activators, Transcriptional Activation, Tumor Suppressor Proteins
Nucleic Acids Res.
Date: Jul. 01, 2005
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