Expression of cFLIPL Determines the Basal Interaction of Bcl‐2 With Beclin‐1 and Regulates p53 Dependent Ubiquitination of Beclin‐1 During Autophagic Stress

Abstract

Autophagy and apoptosis are two different physiological processes, which is required for the maintenance of cellular homeostasis. The apoptosis associated proteins such as Bcl‐2 and p53 have a close association with autophagic proteins HMGB1 and Beclin‐1 to modulate autophagic signaling. We demonstrate here the involvement of anti‐apoptotic protein cFLIP L in the regulation of autophagy during cellular stress. We found that ectopic expression of cFLIP L decreases the sensitivity of HEK 293T cells against rapamycin and H 2 O 2 induced autophagic stress. Notably, the selective knockdown of cFLIP L augments autophagic stress in the cells accompanied with JNK1 activation and p53 dependent ubiquitination of Beclin‐1. However, re‐expression of cFLIP L in cFLIP knockdown cells restores autophagic equilibrium collectively with reversible effects on JNK1 and Beclin‐1 integrity. The co‐immunoprecipitation analysis suggests that cFLIP L is essential to maintain the canonical interaction of Bcl‐2 with Beclin‐1 to regulate autophagic stress and cell death. Altogether, our findings suggest that expression of cFLIP L regulates the basal interaction of Bcl‐2 with Beclin‐1 and substantiates p53 dependent ubiquitination of Beclin‐1 during autophagic stress to determine the fate of cell death or survival. J. Cell. Biochem. 117: 1757–1768, 2016. © 2015 Wiley Periodicals, Inc.