title: Cullin 3 targets methionine adenosyltransferase IIα for ubiquitylation-mediated degradation and regulates colorectal cancer cell proliferation.
abstract: Cullin 3 (CUL3) serves as a scaffold protein and assembles a large number of ubiquitin ligase complexes. It is involved in multiple cellular processes and plays a potential role in tumor development and progression. In this study, we demonstrate that CUL3 targets methionine adenosyltransferase IIα (MAT IIα) and promotes its proteasomal degradation through the ubiquitylation-mediated pathway. MAT IIα is a key enzyme in methionine metabolism and is associated with uncontrolled cell proliferation in cancer. We presently found that CUL3 down-regulation could rescue folate deprivation-induced MAT IIα exhaustion and growth arrest in colorectal cancer (CRC) cells. Further results from human CRC samples display an inverse correlation between CUL3 and MAT IIα protein levels. Our observations reveal a novel role of CUL3 in regulating cell proliferation by controlling the stability of MAT IIα.
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Minhang Hospital, Fudan University, Shanghai, China.
authors.forename: Zi-Hua
authors.initials: ZH
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Yang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Xiang-Ning
authors.initials: XN
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, China.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Liu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Xu
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Lei
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D005492:Folic Acid / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D057809:HEK293 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008716:Methionine Adenosyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D034622:RNA Interference; D054875:Ubiquitination / Q000187:drug effects / Q000235:genetics
chemical_list: C503645:CUL3 protein, human; D044842:Cullin Proteins; D056572:Histone Deacetylase Inhibitors; D005492:Folic Acid; D008716:Methionine Adenosyltransferase
keywords: MAT IIα; colorectal cancer; cullin 3; folate; ubiquitin