The RNA-binding protein RBPMS1 represses AP-1 signaling and regulates breast cancer cell proliferation and migration
The RNA-binding protein RBPMS1 represses AP-1 signaling and regulates breast cancer cell proliferation and migration
复制标题
RNA结合蛋白RBPMS1抑制AP-1信号传导并调节乳腺癌细胞增殖和迁移
DOI：
10.1016/j.bbamcr.2014.09.022
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发表时间：
2015-01-01
影响因子：
5.1
通讯作者：
Ye, Qinong
中科院分区：
文献类型：
--
作者：
Fu, Jie;Cheng, Long;Ye, Qinong
The activator protein-1 (AP-1) transcription factor complex plays a crucial role in tumor growth and progression. However, how AP-1 transcriptional activity is repressed is not fully understood. Here, we show that RNA-binding protein with multiple splicing 1 (RBPMS1) physically and functionally interacts with AP-1 in vitro and in vivo. The RNA-recognition motif (RRM) and C-terminus of the RBPMS1 isoforms RBPMS1A and RBPMS1C, but not RBPMS1B, interacted with cFos, a member of the AP-1 family that dimerizes with gun to stimulate AP-1 transcriptional activity. RBPMS1 did not associate with Jun proteins. RBPMS1A and RBPMS1C bound to the basic leucine zipper (bZIP) domain of cFos that mediates dimerization of AP-1 proteins. In addition, FtBPMS1A-C interacted with the transcription factor Smad3, which was shown to interact with dun and increase AP-1 transcriptional activity. RBPMS1 inhibited c-Fos or Smad3-mediated AP-1 transactivation and the expression of AP-1 target genes known to be the key regulators of cancer growth and progression, including vascular endothelial growth factor (VEGF) and cyclin D1. Mechanistically, RBPMS1 blocks the formation of the cFos/cJun or Smad3/cJun complex as well as the recruitment of cFos or Smad3 to the promoters of AP-1 target genes. In cultured cells and a mouse xenograft model, RBPMS1 inhibited the growth and migration of breast cancer cells through c-Fos or Smad3. These data suggest that RBPMS1 is a critical repressor of AP-1 signaling and RBPMS1 activation may be a useful strategy for cancer treatment. (C) 2014 Elsevier B.V. All rights reserved.
