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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

c-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP

Su-Yan Wang1, Mihail Iordanov, Qinghong Zhang

  • 1Vollum Institute and Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, Oregon 97239, USA.

The Journal of Biological Chemistry
|September 21, 2006
PubMed

Insights

Genetic knockout of carboxyl-terminal-binding protein (CtBP) increases apoptosis. This study shows c-Jun NH2-terminal kinase 1 (JNK1) activation degrades CtBP, inducing cancer cell apoptosis, offering a new chemotherapy target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Pathways

Background:

  • Genetic disruption of carboxyl-terminal-binding protein (CtBP) leads to increased apoptosis.
  • Cellular CtBP levels are hypothesized to regulate apoptosis propensity.
  • Homeodomain-interacting protein kinase 2 (HIPK2) was previously identified as a CtBP regulator.

Purpose of the Study:

  • To investigate the role of c-Jun NH2-terminal kinase 1 (JNK1) in regulating CtBP levels and apoptosis.
  • To determine if JNK1-mediated CtBP degradation induces apoptosis in human lung cancer cells.
  • To explore potential therapeutic strategies targeting CtBP degradation in cancer.

Main Methods:

  • Investigated the effect of JNK1 activation on CtBP phosphorylation and degradation in human lung cancer cells.
  • Utilized UV irradiation and cisplatin to activate the JNK1 pathway.
  • Assessed CtBP levels and apoptosis induction in response to JNK1 activation and deficiency.
  • Examined the role of the proteasome-mediated pathway in CtBP degradation.

Main Results:

  • JNK1 activation triggers CtBP phosphorylation on Ser-422 and subsequent proteasomal degradation.
  • This degradation induces p53-independent apoptosis in human lung cancer cells.
  • UV irradiation and cisplatin-induced JNK1 activation reduce cellular CtBP levels.
  • JNK1 deficiency prevents CtBP degradation and apoptosis induction.

Conclusions:

  • JNK1-mediated degradation of CtBP represents a novel mechanism for inducing apoptosis.
  • Targeting the JNK1-CtBP pathway offers a potential therapeutic strategy for cancers, particularly those lacking p53.
  • This finding provides a new avenue for chemotherapy development in specific cancer types.

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