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p62/SQSTM1 is involved in caspase‐8 associated cell death induced by proteasome inhibitor MG132 in U87MG cells
Author(s) -
Zeng Ruixia,
Zhang YiBo,
Fan Yu,
Wu GeLi
Publication year - 2014
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10311
Subject(s) - mg132 , autophagy , proteasome inhibitor , programmed cell death , apoptosis , proteasome , caspase , cancer research , microbiology and biotechnology , biology , chemistry , biochemistry
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.