Tripartite motif-containing protein 45 (TRIM45) belongs to a large family of RING-finger-containing E3 ligases, which are highly expressed in the brain. However, little is known regarding the role of TRIM45 in cancer biology, especially in human glioma. Here, we report that TRIM45 expression is significantly reduced in glioma tissue samples. Overexpression of TRIM45 suppresses proliferation and tumorigenicity in glioblastoma cells in vitro and in vivo. In addition, CRISPR/Cas9-mediated knockout of TRIM45 promotes proliferation and inhibits apoptosis in glioblastoma cells. Further mechanistic analyses show that TRIM45 interacts with and stabilizes p53. TRIM45 conjugates K63-linked polyubiquitin chain to the C-terminal six lysine residues of p53, thereby inhibiting the availability of these residues to the K48-linked polyubiquitination that targets p53 for degradation. These findings suggest that TRIM45 is a novel tumor suppressor that stabilizes and activates p53 in glioma.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [91629101, 31522018, 81302197]; National Key Basic Research Program of ChinaNational Basic Research Program of China [2015CB859800, 2014CB910800, 2014CB745203]; Guangdong Natural Science Funds for Distinguished Young Scholar [S2013050014772]; Guangdong Innovative Research Team Program [2011Y035, 201001Y0104687244]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [15lgjc02]; Training Program for Outstanding Young Teachers in Higher Education institutions of Guangdong Province [YQ2015001]; NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [CA101795, DA030338]; NIDA, NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA); Jiangsu Provincial Special Programe of Medical Science [BL2014035]; Changzhou Science and Technology Support Program [CE20165048]; Changzhou High-Level Medical Talents Training Project [2016CZBJ006]; Changzhou Municipal Commisions of Health and Family Planning Major Scientific and Technological Project [ZD201620]
语种：
外文
被引次数：
WOS：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区生物
小类|3 区细胞生物学
最新[2023]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Sun Yat Sen Univ, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China;[2]Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Guangzhou 510080, Guangdong, Peoples R China;
通讯作者：
通讯机构：[2]Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Guangzhou 510080, Guangdong, Peoples R China;[3]Sun Yat Sen Univ, Minist Educ, Key Lab Gene Engn, State Key Lab Biocontrol,Sch Life Sci, Guangzhou 510006, Guangdong, Peoples R China;[4]Soochow Univ, Affiliated Hosp 3, Modern Med Res Ctr, 185 Juqian Rd, Changzhou 213000, Peoples R China;[5]Houston Methodist Res Inst, Ctr Inflammat & Epigenet, 6670 Betner Ave, Houston, TX 77096 USA;[6]Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Eastern Campus,Room 320,Bldg Sch Life Sci, Guangzhou 510006, Guangdong, Peoples R China
推荐引用方式(GB/T 7714)：
Zhang Jindong,Zhang Chuanxia,Cui Jun,et al.TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination[J].CELL DEATH & DISEASE.2017,8:-.doi:10.1038/cddis.2017.149.
APA：
Zhang, Jindong,Zhang, Chuanxia,Cui, Jun,Ou, Jiayu,Han, Jing...&Wang, Rong-Fu.(2017).TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination.CELL DEATH & DISEASE,8,
MLA：
Zhang, Jindong,et al."TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination".CELL DEATH & DISEASE 8.(2017):-
生物学