NPM-RAR binding to TRADD selectively inhibits caspase activation, while allowing activation of NFκB and JNK

Leukemia & Lymphoma
Anuja ChattopadhyayRobert L Redner

Abstract

The t(5;17) variant of acute promeylocytic leukemia (APL) expresses a fusion of nucleophosmin (NPM) with the retinoic acid receptor alpha (RARA). We have previously shown that NPM-RAR is a binding partner of the tumor necrosis factor (TNF) receptor type-I-associated DEATH domain protein, TRADD. Binding of TNF to its receptor, TNF-R, induces recruitment of TRADD, and subsequent recruitment of a cascade of proteins that ultimate activate caspase 3, nuclear factor κB (NFκB) and c-Jun N-terminal kinase (JNK). We have previously shown that NPM-RAR interaction with TRADD blocks TNF activation of caspase 3, caspase 8, poly(ADP-ribose) polymerase (PARP) cleavage and, ultimately, apoptosis. We now report that NPM-RAR expression is permissive for TNF activation of NFκB and JNK. We propose that inhibition of TNF activation of apoptosis, while preserving TNF activation of NFκB and JNK pathways that stimulate cell growth and survival, represents a novel mechanism through which NPM-RAR contributes to development of the leukemic phenotype.

References

May 1, 1992·Genes & Development·M KretzschmarR G Roeder
Jun 5, 2002·The Journal of Cell Biology·Michael MorganAndrew Thorburn
Mar 26, 2003·Cell Death and Differentiation·H WajantP Scheurich
Apr 17, 2004·The Journal of Biological Chemistry·Sanjit K DharDaret K St Clair
Jul 25, 2009·Nature Reviews. Cancer·Erwin F Wagner, Angel R Nebreda
Jan 15, 2011·The FEBS Journal·Harald Wajant, Peter Scheurich
May 9, 2012·Nature Cell Biology·Iok In Christine ChioTak Wah Mak
Nov 5, 2013·Leukemia Research·Elizabeth A RushRobert L Redner
Jul 19, 2014·Molecular Cancer Research : MCR·Anuja ChattopadhyayRobert L Redner

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Citations

Jan 13, 2016·Leukemia & Lymphoma·Erin M SwaneyRobert L Redner
Dec 8, 2019·Cellular and Molecular Life Sciences : CMLS·Federica FusellaMara Brancaccio

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