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JMJD4 promotes tumor progression via inhibition of the PDCD5-TP53 pathway

Hyunsik Kim1, Subhin Jang2, Soo Yeon Lee1

  • 1Department of Biochemistry and Molecular Biology, Severance Medical Research Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea.

BMB Reports
|November 20, 2024
PubMed

Insights

Jumonin domain-containing protein 4 (JMJD4) interacts with programmed cell death 5 (PDCD5), suppressing cancer cell death and promoting proliferation. JMJD4 indicates poor prognosis in colon and lung cancers, suggesting it as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Regulation

Background:

  • Programmed cell death 5 (PDCD5) is crucial for regulating cell death and tumor suppression.
  • Understanding PDCD5 regulation is vital for the TP53-signaling pathway, especially its stability and nuclear translocation.
  • The precise mechanisms governing PDCD5 function require further elucidation.

Purpose of the Study:

  • To identify novel PDCD5-interacting proteins.
  • To investigate the functional role of identified interactors in cancer cell death and proliferation.
  • To explore the clinical relevance of these interactions in human cancers.

Main Methods:

  • Liquid chromatography-mass spectrometry (LC-MS) for protein-protein interaction identification.
  • Colony-formation assays to assess cell proliferation and chemo-resistance.
  • Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases for clinical correlation.

Main Results:

  • Jumonin domain-containing protein 4 (JMJD4) was identified as a direct interactor of PDCD5.
  • JMJD4 enhances cancer cell proliferation and chemo-resistance under genotoxic stress.
  • JMJD4 suppresses PDCD5 protein levels, leading to decreased expression of TP53-related apoptotic genes (BAX, PUMA).
  • JMJD4 expression correlates with poor prognosis in colon and lung cancer patients.

Conclusions:

  • JMJD4 directly interacts with PDCD5 and negatively regulates cancer cell death.
  • JMJD4's role in promoting proliferation and chemo-resistance highlights its significance in cancer development.
  • JMJD4 represents a potential therapeutic target for various cancer types.

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