Nuclear factor-kappaB dimer exchange promotes a p21(waf1/cip1) superinduction response in human T leukemic cells

Molecular Cancer Research : MCR
Pei-Yun Chang, Shigeki Miyamoto

Abstract

The nuclear factor-kappaB (NF-kappaB)/Rel transcription factors are recognized as critical apoptosis regulators. We reported previously that NF-kappaB contributes to chemoresistance of CEM human T leukemic cells in part through its ability to induce p21(waf1/cip1). Here, we provide evidence that sequential NF-kappaB-activating signals induce heightened NF-kappaB DNA binding and p21(waf1/cip1) induction in CEM and additional T leukemic cell lines. This response arises from exceedingly low basal expression of the p105/p50 NF-kappaB subunit encoded by the NFKB1 gene in these cell lines. An initial NF-kappaB activation event enhances the recruitment of p65 and ELF1 to the NFKB1 promoter, leading to p65- and ELF1-dependent synthesis of p105/p50, which promotes an exchange of NF-kappaB complexes to p50-containing complexes with an increased DNA-binding activity to certain NF-kappaB target elements. Subsequent stimulation of these cells with an anticancer agent, etoposide, results in augmented NF-kappaB-dependent p21(waf1/cip1) induction and increased chemoresistance of the leukemia cells. Thus, we propose that low basal NFKB1 expression coupled with sequential NF-kappaB activation events can promote increased chemoresistance in certa...Continue Reading

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Citations

Jul 4, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Zhao-Hui Wu, Shigeki Miyamoto
Sep 10, 2011·The Journal of Biological Chemistry·Carwyn DaviesRichard B Lock
Aug 27, 2010·Journal of Virology·Mei XuDenise A Galloway
Nov 1, 2006·Molecular and Cellular Biology·Craig M BerchtoldShigeki Miyamoto
Mar 31, 2018·Biomedicines·Georgios S MarkopoulosEvangelos Kolettas
Nov 23, 2006·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·María-Teresa Fernández-FiguerasAurelio Ariza
May 5, 2012·PloS One·Sílvia Cristina Paiva AlmeidaRobert Michael Evans Parkhouse
Aug 30, 2008·Journal of Cellular Biochemistry·Karishma M FernandesRon F Morrison
Jun 17, 2006·Cancer Research·Pei-Yun ChangShigeki Miyamoto

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis