Alterations of BRMS1-ARID4A interaction modify gene expression but still suppress metastasis in human breast cancer cells.

The Journal of Biological Chemistry
Douglas R HurstDanny R Welch

Abstract

The BRMS1 metastasis suppressor interacts with the protein AT-rich interactive domain 4A (ARID4A, RBBP1) as part of SIN3.histone deacetylase chromatin remodeling complexes. These transcriptional co-repressors regulate diverse cell phenotypes depending upon complex composition. To define BRMS1 complexes and their roles in metastasis suppression, we generated BRMS1 mutants (BRMS1(mut)) and mapped ARID4A interactions. BRMS1(L174D) disrupted direct interaction with ARID4A in yeast two-hybrid genetic screens but retained an indirect association with ARID4A in MDA-MB-231 and -435 human breast cancer cell lines by co-immunoprecipitation. Deletion of the first coiled-coil domain (BRMS1(DeltaCC1)) did not disrupt direct interaction in yeast two-hybrid screens but did prevent association by co-immunoprecipitation. These results suggest altered complex composition with BRMS1(mut). Although basal transcription repression was impaired and the pro-metastatic protein osteopontin was differentially down-regulated by BRMS1(L174D) and BRMS1(DeltaCC1), both down-regulated the epidermal growth factor receptor and suppressed metastasis in MDA-MB-231 and -435 breast cancer xenograft models. We conclude that BRMS1(mut), which modifies the composition...Continue Reading

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Citations

Jun 21, 2008·Clinical & Experimental Metastasis·Brandon J MetgeLalita A Shevde
Oct 9, 2008·Clinical & Experimental Metastasis·Douglas R HurstDanny R Welch
Jul 31, 2008·The Journal of Biological Chemistry·Kedar S VaidyaDanny R Welch
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Jul 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael D ClarkIshwar Radhakrishnan
Jul 23, 2011·Journal of Molecular Biology·Mercedes Spínola-AmilibiaJerónimo Bravo
Aug 11, 2011·FEBS Letters·Douglas R Hurst, Danny R Welch
Jul 9, 2009·International Journal of Cancer. Journal International Du Cancer·Mick D EdmondsDanny R Welch
Sep 11, 2010·Journal of Cellular Biochemistry·José RiveraJerónimo Bravo
Jan 3, 2014·International Journal of Cancer. Journal International Du Cancer·Tatiana CajusoPia Vahteristo
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Mar 8, 2018·International Journal of Oncology·Dalin DiJiyu Ju
Apr 2, 2020·Cancer Metastasis Reviews·Rosalyn C Zimmermann, Danny R Welch
Feb 13, 2016·Oncology Letters·Emily Falk LibbyDouglas R Hurst
Feb 1, 2011·The International Journal of Biological Markers·Xiuping ChenYitao Wang
Jun 25, 2020·Cancer Metastasis Reviews·Belinda J Petri, Carolyn M Klinge
Jan 23, 2019·Biomolecular NMR Assignments·Weibin GongYingang Feng
Aug 29, 2020·Cancer Research·Piotr PrzanowskiSanchita Bhatnagar
Mar 7, 2021·The Journal of Biological Chemistry·Jie RenYingang Feng
Sep 11, 2021·Journal of Molecular Biology·Weibin GongYingang Feng
Nov 18, 2021·PloS One·Rosalyn C ZimmermannDanny R Welch

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