Activation of NFkappaB and Ub-proteasome pathway during apoptosis induced by a serum factor is mediated through the upregulation of the 26S proteasome subunits

Apoptosis : an International Journal on Programmed Cell Death
S Singh, A Khar

Abstract

We have been investigating differential gene expression associated with apoptosis in AK-5 cells (a spontaneously regressing rat histiocytoma) and have observed catalytic subunits beta 7 and alpha 5 of the 26S proteasome and ubiquitin to be upregulated during apoptosis induced by a variety of agents. The observed elevation in gene expression was parallel to a comparable increase in the cytosolic protein expression of the proteasome and ubiquitin and a markedly amplified increase in the proteasome activity. Inhibition of the increase in gene expression resulted in the inhibition of the rise in the proteasome activity subsequently leading to an inhibition of apoptosis. Similarly, pretreatment with proteasome inhibitors, MG132 and lactacystin, resulted in a significant inhibition of apoptosis pointing to the requirement of a highly active protein degradation machinery during apoptosis. The apoptosis inhibitory effect of the proteasome inhibitors involved an inhibition of the activation of various initiator and effector caspases but was independent of any changes in the mitochondrial membrane depolarization and cytochrome c release associated with apoptosis. Inhibition of proteasome activity or its upstream PI3 kinase activity inhib...Continue Reading

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Citations

Dec 6, 2007·BMC Biochemistry·Burkhardt Dahlmann
Dec 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sarvjeet SinghPradeep P A Mammen
Jan 24, 2012·Electromagnetic Biology and Medicine·Adamantia F FragopoulouLukas H Margaritis
Dec 21, 2010·Journal of Neurochemistry·Anna Moszczynska, Bryan K Yamamoto
Dec 30, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yinghua LiChaoyang Dai
Apr 23, 2013·Toxicology Letters·Sven DänickeHermann-Josef Rothkötter
Jul 11, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Sakshi MishraMukul Das
Oct 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrea Sartore-BianchiLuciano Mutti

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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