title: p62/SQSTM1 is involved in caspase-8 associated cell death induced by proteasome inhibitor MG132 in U87MG cells.
abstract: Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. Proteasome inhibitors are emerging as a new class of anti-glioma agents; however, the mechanisms of their killing malignant cells are still unclear. We treated U87MG cells with the proteasome inhibitor MG132 and found that cell death correlated with caspase-8 activation and autophagy protein p62/SQSTM1.To explore the role of autophagy and p62/SQSTM1 in MG132-induced cancer cell death, we measured the alteration of MG132's cytotoxicity by autophagy inhibition, autophagy induction or variation of p62/SQSTM1 gene expression. Autophagy was activated upon MG132 treatment for short periods, while inhibition of autophagy aggravated MG132-induced cell death followed by high levels of p62/SQSTM1 and active caspase-8 (p18). Moreover, U87MG cell death was dependent on p62/SQSTM1, and its function required its C-terminus UBA domain to attenuate the MG132-induced cell death. The results suggest that p62/SQSTM1 is a potential contributor in determining the fate of U87MG cells deficient in proteolytic activity.
authors.affiliation: Department of Human Anatomy, School of Basic Medical Sciences, Liaoning Medical University, Jinzhou, 121001, China.
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Zeng
authors.forename: Yi-Bo
authors.initials: YB
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
authors.forename: Ge-Li
authors.initials: GL
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007976:Leupeptins / Q000633:toxicity*; D011480:Protease Inhibitors / Q000633:toxicity*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000071456:Sequestosome-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007976:Leupeptins; D011480:Protease Inhibitors; D034741:RNA, Small Interfering; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D053181:Caspase 8; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: MG132; U87MG; caspase-8; p62; proteasome inhibition