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Updated: Oct 5, 2025

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JNK-dependent phosphorylation and nuclear translocation of EGR-1 promotes cardiomyocyte apoptosis

Jinrun Zhou1, Yujuan Yao1, Jiaojiao Zhang1

  • 1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, 266237, People's Republic of China.

Apoptosis : an International Journal on Programmed Cell Death
|February 1, 2022
PubMed

Insights

Nuclear EGR-1 promotes cardiomyocyte apoptosis via JNK-mediated phosphorylation, offering a new therapeutic target for cardiovascular diseases like ischemia and hyperlipemia.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Cell Death Mechanisms

Background:

  • Myocardial apoptosis from ischemia and hyperlipemia contributes significantly to cardiovascular disease mortality.
  • Early growth response protein 1 (EGR-1) is implicated in cardiomyocyte apoptosis under stress.
  • The nuclear translocation mechanism and universal role of EGR-1 in cardiomyocyte apoptosis remain unclear.

Purpose of the Study:

  • To elucidate the mechanism of nuclear entry for EGR-1 in cardiomyocytes.
  • To investigate the universal pro-apoptotic function of nuclear EGR-1 (nEGR-1).
  • To identify downstream targets of nEGR-1 involved in promoting cardiomyocyte apoptosis.

Main Methods:

  • Analysis of EGR-1 phosphorylation sites and nuclear localization signals.
  • Construction and utilization of mutant plasmids to study EGR-1 nuclear translocation.
  • Genetic methods to explore the pro-apoptotic effects of nEGR-1 and its downstream targets.

Main Results:

  • Nuclear translocation of EGR-1 is dependent on Ser501 phosphorylation, regulated by JNK.
  • nEGR-1 exhibits a universal pro-apoptotic function in cardiomyocytes.
  • EGR-1 positively regulates the mRNA levels of apoptosis-related factors: ATF2, CTCF, HAND2, and ELK1.

Conclusions:

  • The study reveals a novel mechanism for nEGR-1 nuclear import in cardiomyocytes.
  • nEGR-1 universally promotes cardiomyocyte apoptosis, potentially through regulating ATF2, CTCF, HAND2, and ELK1.
  • These findings provide a new therapeutic target for cardiovascular diseases characterized by cardiomyocyte apoptosis.
Keywords:
EGR-1JNKPalmitate acidPhosphorylationSphingosylphosphorylcholine

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