Home » Key Scientific Articles » Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apoptosis in U87MG cells.

Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apoptosis in U87MG cells.

Zhang YB, Gong JL, Xing TY, Zheng SP, Ding W.

Cell Death Dis. 2013 Mar 21;4:e550.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

 

Abstract

 

HAMLET is a complex of oleic acids and decalcified {Alpha}-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo.Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker ofautophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

 

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