title: Cbl-b-dependent degradation of FLIP(L) is involved in ATO-induced autophagy in leukemic K562 and gastric cancer cells.
abstract: Various molecular mechanisms are involved in the efficacy of arsenic trioxide (ATO) against malignant hematologic and some solid tumors. FLICE-like inhibitory protein (FLIP) is an inhibitor of apoptosis mediated by death receptors. In this study, we identified a new link between the down-regulation of cellular FLIP(L) and ATO-induced autophagy. ATO induced the degradation of FLIP(L) in K562 and MGC803 cells, which was mediated by the ubiquitin-proteasome pathway. Moreover, the casitas B-lineage lymphoma-b (Cbl-b) was involved in this process, which interacted with FLIP(L) and promoted proteasomal degradation of FLIP(L). Our findings lead to a better understanding of the mechanism of action of ATO, and suggest that a novel signaling pathway is required for ATO-induced autophagy in K562 and MGC803 cells.
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinglei
authors.initials: J
authors.lastname: Qu
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Huachuan
authors.initials: H
authors.lastname: Zheng
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Qu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology*; D001483:Base Sequence; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001152:Arsenicals; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D010087:Oxides; D034741:RNA, Small Interfering; D025801:Ubiquitin; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl; D046988:Proteasome Endopeptidase Complex; D000077237:Arsenic Trioxide