title: E3 ubiquitin ligase TRIM32 negatively regulates tumor suppressor p53 to promote tumorigenesis.
abstract: Tumor suppressor p53 has a key role in maintaining genomic stability and preventing tumorigenesis through its regulation of cellular stress responses, including apoptosis, cell cycle arrest and senescence. To ensure its proper levels and functions in cells, p53 is tightly regulated mainly through post-translational modifications, such as ubiquitination. Here, we identified E3 ubiquitin ligase TRIM32 as a novel p53 target gene and negative regulator to regulate p53-mediated stress responses. In response to stress, such as DNA damage, p53 binds to the p53 responsive element in the promoter of the TRIM32 gene and transcriptionally induces the expression of TRIM32 in cells. In turn, TRIM32 interacts with p53 and promotes p53 degradation through ubiquitination. Thus, TRIM32 negatively regulates p53-mediated apoptosis, cell cycle arrest and senescence in response to stress. TRIM32 is frequently overexpressed in different types of human tumors. TRIM32 overexpression promotes cell oncogenic transformation and tumorigenesis in mice in a largely p53-dependent manner. Taken together, our results demonstrated that as a novel p53 target and a novel negative regulator for p53, TRIM32 has an important role in regulation of p53 and p53-mediated cellular stress responses. Furthermore, our results also revealed that impairing p53 function is a novel mechanism for TRIM32 in tumorigenesis.
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 1] Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA [2] Department of Breast Surgery, Qilu Hospital, Shandong University, Ji'nan, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: P
authors.initials: P
authors.lastname: Ly
authors.affiliation: Center for Systems Biology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: V
authors.initials: V
authors.lastname: Belyi
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Young
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004249:DNA Damage; D006801:Humans; D051379:Mice; D014157:Transcription Factors / Q000235:genetics*; D000070584:Tripartite Motif Proteins; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D054875:Ubiquitination
chemical_list: D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D016159:Tumor Suppressor Protein p53; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases