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Differential use of CREB binding protein-coactivator complexes
R Kurokawa1, D Kalafus, M H Ogliastro
1Division of Cellular and Molecular Medicine, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.
Insights
Adenovirus E1A protein inhibits transcription factors. Researchers found E1A inhibits retinoic acid receptor (RAR) function differently than STAT1, by blocking coactivator complex assembly, not targeting the C/H3 domain.
Area of Science:
- Molecular Biology
- Virology
- Cellular Biology
Background:
- CREB binding protein (CBP) is a crucial coactivator for transcription factors.
- Adenovirus early gene product E1A inhibits certain transcription factors by targeting CBP.
- Signal transducer and activator of transcription-1 (STAT1) activation relies on the CBP C/H3 domain, a target for E1A.
Purpose of the Study:
- To investigate the mechanism by which E1A inhibits retinoic acid receptor (RAR) function.
- To determine if the CBP C/H3 domain is involved in RAR transcriptional activation and E1A inhibition.
- To elucidate the differences in CBP domain requirements for RAR and STAT1 transcriptional activation.
Main Methods:
- Investigated the role of the CBP C/H3 domain in RAR-mediated transcription.
- Assessed the impact of E1A on RAR function and CBP coactivator complex formation.
- Compared CBP domain requirements for RAR and STAT1 transcriptional activation.
Main Results:
- The CBP C/H3 domain is not essential for retinoic acid receptor (RAR) function.
- E1A does not inhibit RAR function by targeting the C/H3 domain.
- E1A inhibits RAR by preventing the assembly of CBP-nuclear receptor coactivator complexes.
Conclusions:
- Transcriptional activation by RAR and STAT1 requires different domains of CBP.
- E1A employs distinct mechanisms to inhibit RAR and STAT1, highlighting differential CBP involvement.
- Understanding these differences provides insight into the regulation of nuclear receptor and STAT1 signaling pathways.
Abstract:
CREB binding protein (CBP) functions as an essential coactivator of transcription factors that are inhibited by the adenovirus early gene product E1A. Transcriptional activation by the signal transducer and activator of transcription-1 (STAT1) protein requires the C/H3 domain in CBP, which is the primary target of E1A inhibition. Here it was found that the C/H3 domain is not required for retinoic acid receptor (RAR) function, nor is it involved in E1A inhibition. Instead, E1A inhibits RAR function by preventing the assembly of CBP-nuclear receptor coactivator complexes, revealing differences in required CBP domains for transcriptional activation by RAR and STAT1.