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Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse
1Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021, USA.
Abstract:
The human thyroid hormone receptor-associated protein (TRAP) complex, an earlier described coactivator for nuclear receptors, and an SRB- and MED-containing cofactor complex (SMCC) that mediates activation by Gal4-p53 are shown to be virtually the same with respect to specific polypeptide subunits, coactivator functions, and mechanisms of action (activator interactions). In parallel with ligand-dependent interactions of nuclear receptors with the TRAP220 subunit, p53 and VP16 activation domains interact directly with a newly cloned TRAP80 subunit. These results indicate novel pathways for the function of nuclear receptors and other activators (p53 and VP16) through a common coactivator complex that is likely to target RNA polymerase II. Identification of the TRAP230 subunit as a previously predicted gene product also suggests a coactivator-related transcription defect in certain disease states.
Insights
The thyroid hormone receptor-associated protein (TRAP) complex and the SRB- and MED-containing cofactor complex (SMCC) are the same coactivator. This finding reveals new pathways for nuclear receptor function and potential disease links.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- Nuclear receptors regulate gene expression via coactivators.
- The thyroid hormone receptor-associated protein (TRAP) complex and SRB- and MED-containing cofactor complex (SMCC) were previously described as distinct coactivators.
Purpose of the Study:
- To investigate the relationship between the TRAP complex and SMCC.
- To identify the functional interactions of TRAP subunits with activators like p53 and VP16.
Main Methods:
- Comparative analysis of polypeptide subunits between TRAP and SMCC.
- Investigation of activator interactions with TRAP subunits, including TRAP80.
Main Results:
- The TRAP complex and SMCC are virtually identical, sharing subunits and functions.
- p53 and VP16 activation domains directly interact with the TRAP80 subunit.
- TRAP230 was identified as a known predicted gene product.
Conclusions:
- A common coactivator complex, likely targeting RNA polymerase II, mediates the function of nuclear receptors and other activators.
- The identification of TRAP230 suggests potential coactivator-related transcription defects in certain diseases.