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Updated: Aug 13, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Caspase-3 mediated cleavage of MEKK1 promotes p53 transcriptional activity

David C Zebrowski1, Ralph R Alcendor, Lorrie A Kirshenbaum

  • 1Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, 07103, USA.

Journal of Molecular and Cellular Cardiology
|January 24, 2006
PubMed

Insights

Myocardial ischemia/reperfusion (IR) injury activates the p53 protein, a key factor in myocyte apoptosis. Caspase-3 cleaves MEKK1, promoting p53 activity through JNK-independent pathways.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cell Biology
  • Apoptosis Research

Background:

  • Myocardial ischemia/reperfusion (IR) injury is a significant cause of heart damage.
  • The pro-apoptotic protein p53 plays a role in myocyte apoptosis during IR.
  • The precise signaling pathways leading to p53 activation in IR remain unclear.

Purpose of the Study:

  • To elucidate the mechanism by which IR induces p53 activation.
  • To investigate the role of MEKK1 and caspase-3 in IR-induced p53 signaling.

Main Methods:

  • In vivo and in vitro models of ischemic injury.
  • Analysis of MEKK1 proteolytic cleavage and its dependence on caspase-3.
  • Overexpression studies to assess the impact of MEKK1 cleavage on p53 phosphorylation and transcriptional activity.
  • Investigation of MEKK1's interaction with ATF2 and JNK signaling.

Main Results:

  • MEKK1 undergoes caspase-3 dependent proteolytic cleavage during ischemic injury.
  • Caspase-3 mediated cleavage of MEKK1 enhances p53 phosphorylation and transcriptional activity.
  • Caspase-3 cleavage of MEKK1 abrogates its ability to activate ATF2 and signal JNK.

Conclusions:

  • IR induces caspase-3 mediated cleavage of MEKK1.
  • This cleavage promotes p53 transcriptional activity via JNK-independent mechanisms.
  • The MEKK1-caspase-3-p53 axis contributes to pathological insults, including myocyte apoptosis, during IR injury.

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