Regulation of the antiapoptotic protein cFLIP by the glucocorticoid Dexamethasone in ALL cells.

ABSTRACT: We recently reported that the Smac mimetic BV6 and glucocorticoids, e.g. Dexamethasone (Dexa), synergize to induce cell death in acute lymphoblastic leukemia (ALL) in vitro and in vivo. Here, we discover that this synergism involves Dexa-stimulated downregulation of cellular FLICE-like inhibitory protein (cFLIP) in ALL cells. Dexa rapidly decreases cFLIP_L protein levels, which is further enhanced by addition of BV6. While attenuating the activation of non-canonical nuclear factor-kappaB (NF-κB) signaling by BV6, Dexa suppresses cFLIP_L protein but not mRNA levels pointing to a transcription-independent downregulation of cFLIP_L by Dexa. Analysis of protein degradation pathways indicates that Dexa causes cFLIP_L depletion independently

SUBMITTER: Kleinesudeik L 

PROVIDER: S-EPMC5893259 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature