title: Cancer-testis antigen HCA587/MAGE-C2 interacts with BS69 and promotes its degradation in the ubiquitin-proteasome pathway.
abstract: HCA587, also known as MAGE-C2, belonging to the MAGE gene family which is characterized by a conserved MAGE Homology Domain, is active in various types of tumors and silent in normal tissues except in male germ-line cells. The biological function of HCA587 is largely unknown. To analyze it, we attempted to identify protein partners of HCA587. We immunopurified HCA587-containing complex from HEK293 cells and identified BS69, a potential tumor suppressor, as an associated protein by mass spectrometry, and the following Immunoprecipitation and GST pull-down assays confirmed HCA587 interaction with BS69. Interestingly, overexpression of HCA587 promoted ubiquitination and the proteasomal degradation of BS69 whereas knockdown of endogenous HCA587 increased the protein level of BS69. Consistent with a functional role for BS69 in negatively regulating LMP1-induced NF-κB activation, overexpression of HCA587 resulted in a significant enhancement of LMP1-induced IL-6 production. These data indicate that HCA587 is a new negative regulator of BS69.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Shen
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, Beijing, China. Electronic address: yinyanhui@bjmu.edu.cn.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D003598:Cytoskeletal Proteins / Q000494:pharmacology; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D060588:LIM Domain Proteins / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D060588:LIM Domain Proteins; C405429:MAGEC2 protein, human; D009363:Neoplasm Proteins; C484380:PDLIM7 protein, human; C094763:ZMYND11 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: BS69; Cancer–testis antigen; HCA587; Ubiquitination