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

S. Singh, A. Khar

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 inhibited NFκB translocation thereby suppressing apoptosis, which highlights the requirement of NFκB activation for completion of apoptosis in AK-5 cells. Hence, the apoptosis associated induction of the Ub-proteasome pathway components and the proteasome activity suggests that the proteasome, in its capacity as an efficient protein degradation complex, plays an important role in the successful execution of apoptosis.

Original languageEnglish (US)
Pages (from-to)845-859
Number of pages15
JournalApoptosis
Volume11
Issue number5
DOIs
StatePublished - May 1 2006

Fingerprint

Proteasome Endopeptidase Complex
Up-Regulation
Chemical activation
Apoptosis
Serum
Gene expression
Proteasome Inhibitors
Ubiquitin
Gene Expression
Proteolysis
ATP dependent 26S protease
Histiocytoma
Initiator Caspases
Effector Caspases
Degradation
Proteins
Depolarization
Mitochondrial Membranes
Cytochromes c
Phosphatidylinositol 3-Kinases

Keywords

  • Apoptosis
  • Caspases
  • NFκB
  • Proteasome
  • Proteasome inhibitors
  • Ubiquitin
  • Upregulation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

Activation of NFκB and Ub-proteasome pathway during apoptosis induced by a serum factor is mediated through the upregulation of the 26S proteasome subunits. / Singh, S.; Khar, A.

In: Apoptosis, Vol. 11, No. 5, 01.05.2006, p. 845-859.

Research output: Contribution to journalArticle

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