Premium
Scaffold attachment factor B (SAFB)1 and SAFB2 cooperatively inhibit the intranuclear mobility and function of ERα
Author(s) -
Hashimoto Takashi,
Matsuda KenIchi,
Kawata Mitsuhiro
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24182
Subject(s) - transcription factor , microbiology and biotechnology , repressor , immunoprecipitation , nuclear transport , scaffold protein , chemistry , hek 293 cells , transcription (linguistics) , estrogen receptor alpha , nuclear localization sequence , biology , estrogen receptor , cell nucleus , nucleus , biochemistry , signal transduction , receptor , genetics , gene , linguistics , philosophy , cancer , breast cancer
Estrogen receptor alpha (ERα) plays a key role in physiological and pathophysiological processes as a ligand‐activated transcriptional factor that is regulated by cofactors. ERα‐mediated transcriptional regulation is closely correlated with the mobility of ERα in the nucleus in association with the nuclear matrix, the framework for nuclear events including transcription. However, the relationship between ERα mobility and the cofactors of ERα is unclear. Scaffold attachment factor B1 (SAFB1) and its paralog SAFB2 are nuclear matrix binding proteins that have been characterized as ERα corepressors. Here, using chimeric fluorescent proteins (FPs), we show that SAFB1 and SAFB2 colocalize with ERα in the nucleus of living cells after 17β‐estradiol (E2) treatment. Co‐immunoprecipitation (co‐IP) experiments indicated that ERα interacts with both SAFB1 and SAFB2 in the presence of E2. Fluorescence recovery after photobleaching analysis revealed that SAFB1 and SAFB2 each decrease ERα mobility, and interestingly, coexpression of SAFB1 and SAFB2 causes a synergistic reduction in ERα dynamics under E2 treatment. In accordance with these mobility changes, ERα‐mediated transcription and proliferation are cooperatively inhibited by SAFB1 and SAFB2. These results indicate that SAFB1 and SAFB2 are crucial repressors for ERα dynamics in association with the nuclear matrix and that their synergistic regulation of ERα mobility is sufficient for inhibiting ERα function. J. Cell. Biochem. 113: 3039–3050, 2012. © 2012 Wiley Periodicals, Inc.