title: The RNA-binding protein RBPMS1 represses AP-1 signaling and regulates breast cancer cell proliferation and migration.
abstract: 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 cJun 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, RBPMS1A-C interacted with the transcription factor Smad3, which was shown to interact with cJun 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.
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China; Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.affiliation: School of Life Sciences, Shandong University, Shandong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Fujian Center for Disease Control and Prevention, Fujian, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Interventional Radiology, The Affiliated First Hospital, Fujian Medical University, Fujian, China. Electronic address: yunping1448@sina.com.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China. Electronic address: yeqn66@yahoo.com.
authors.forename: Qinong
authors.initials: Q
authors.lastname: Ye
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D016601:RNA-Binding Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; C101827:RBPMS protein, human; D016601:RNA-Binding Proteins; D051900:Smad3 Protein; D018808:Transcription Factor AP-1
keywords: AP-1; Breast cancer; Cell growth; Cell migration; Protein–protein interaction; RBPMS1