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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

Regulation of apoptotic c-Jun N-terminal kinase signaling by a stabilization-based feed-forward loop

Zhiheng Xu1, Nikolay V Kukekov, Lloyd A Greene

  • 1Department of Pathology and Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, New York 10032, USA. zx18@columbia.edu

Molecular and Cellular Biology
|November 2, 2005
PubMed

Insights

Apoptotic stimuli stabilize key proteins in the c-Jun N-terminal kinases (JNK) pathway, including POSH and MLKs. This stabilization creates a feed-forward loop that amplifies JNK signaling, promoting programmed cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The c-Jun N-terminal kinases (JNK) pathway is crucial for inducing apoptosis.
  • Mechanisms regulating JNK pathway activation by apoptotic stimuli are not fully understood.

Purpose of the Study:

  • To elucidate how apoptotic stimuli engage the JNK pathway.
  • To identify mechanisms suppressing JNK signaling in viable cells.

Main Methods:

  • Investigated changes in endogenous cellular levels of JNK pathway components.
  • Assessed the role of POSH, mixed lineage kinases (MLKs), and JNK interacting protein 1.
  • Examined protein stabilization as a regulatory mechanism.

Main Results:

  • Apoptotic stimuli increase levels of POSH, MLKs, and JNK interacting protein 1.
  • This increase is mediated by protein stabilization.
  • The effect requires POSH and activation of MLKs and JNKs.

Conclusions:

  • Apoptotic stimuli activate a self-amplifying, feed-forward loop in the JNK pathway.
  • Protein stabilization of pathway components contributes to JNK activation and cell death.

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