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Published on: December 26, 2016
Breast cancer metastasis suppressor 1 (BRMS1) is stabilized by the Hsp90 chaperone
Douglas R Hurst1, Alka Mehta, Blake P Moore
1Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Abstract:
Breast cancer metastasis suppressor 1 (BRMS1) is a member of the mSin3-HDAC transcription co-repressor complex. However, the proteins associated with BRMS1 have not been fully identified. Yeast two-hybrid screen, immuno-affinity chromatography, and co-immunoprecipitation experiments were performed to identify BRMS1 interacting proteins (BIPs). In addition to known core mSin3 transcriptional complex components RBBP1 and mSDS3, BRMS1 interacted with other proteins including three chaperones: DNAJB6 (MRJ), Hsp90, and Hsp70. Hsp90 is a known target of HDAC6 and reversible acetylation is one of the mechanisms that is implicated in regulation of Hsp90 chaperone complex activity. BRMS1 interacted with class II HDACs, HDAC 4, 5, and 6. We further found that BRMS1 is stabilized by Hsp90, and its turnover is proteasome dependent. The stability of BRMS1 protein may be important in maintaining the functional role of BRMS1 in metastasis suppression.
Insights
Breast cancer metastasis suppressor 1 (BRMS1) interacts with chaperones like Hsp90 and HDACs. Hsp90 stabilizes BRMS1, suggesting protein stability is key for its metastasis suppression role.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Breast cancer metastasis suppressor 1 (BRMS1) is a key component of the mSin3-HDAC transcriptional co-repressor complex.
- The full spectrum of proteins interacting with BRMS1 remains incompletely characterized.
- Understanding BRMS1 interactions is crucial for elucidating its role in metastasis suppression.
Purpose of the Study:
- To identify novel proteins that interact with Breast cancer metastasis suppressor 1 (BRMS1).
- To investigate the relationship between BRMS1, heat shock proteins (Hsp90, Hsp70), and histone deacetylases (HDACs).
- To determine the factors regulating BRMS1 protein stability.
Main Methods:
- Yeast two-hybrid screening to identify potential interacting partners.
- Immuno-affinity chromatography to isolate BRMS1-associated proteins.
- Co-immunoprecipitation assays to confirm protein-protein interactions.
- Analysis of BRMS1 stability and proteasomal degradation pathways.
Main Results:
- Identified novel BRMS1-interacting proteins (BIPs), including chaperones DNAJB6 (MRJ), Hsp90, and Hsp70.
- Confirmed interactions between BRMS1 and class II HDACs (HDAC4, HDAC5, HDAC6).
- Demonstrated that Hsp90 stabilizes BRMS1, and its degradation is proteasome-dependent.
Conclusions:
- BRMS1 engages with a network of chaperones and HDACs, expanding its known functional complex.
- Hsp90-mediated stabilization of BRMS1 is a critical factor for its function.
- The stability of BRMS1 protein is essential for its efficacy in suppressing cancer metastasis.
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