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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Zhang G,Liu J,Zhang Y,Qu J,Xu L,Zheng H,Liu Y,Qu X

doi

10.1016/j.febslet.2012.07.067

subject

Has Abstract

pub_date

2012-09-21 00:00:00

pages

3104-10

issue

19

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(12)00635-7

journal_volume

586

pub_type

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