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Updated: Oct 26, 2025

Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
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Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry

Published on: May 17, 2016

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Methylation of dual-specificity phosphatase 4 controls cell differentiation

Hairui Su1, Ming Jiang2, Chamara Senevirathne3

  • 1Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Cell Reports
|July 28, 2021
PubMed

Insights

Dual-specificity phosphatase 4 (DUSP4) inactivates p38 kinase, promoting megakaryocyte differentiation. This pathway is crucial for treating myelodysplastic syndrome-related thrombocytopenia.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Hematology

Background:

  • Mitogen-activated protein kinases (MAPKs) regulate cell differentiation.
  • Dual-specificity phosphatases (DUSPs) inactivate MAPKs.
  • DUSP4's role in megakaryocyte differentiation is not fully understood.

Purpose of the Study:

  • To identify the specific DUSP that inactivates p38 kinase during megakaryocyte differentiation.
  • To elucidate the regulatory mechanism of DUSP4.
  • To explore the therapeutic potential of targeting the DUSP4-p38 axis in myelodysplastic syndrome (MDS).

Main Methods:

  • Knockdown screening and single-cell transcriptional analysis.
  • Investigated PRMT1-mediated methylation and HUWE1-mediated ubiquitination of DUSP4.
  • Analyzed p38 MAPK and PRMT1 levels in MDS patients.

Main Results:

  • DUSP4 specifically inactivates p38 kinase, promoting megakaryocyte differentiation.
  • PRMT1-mediated methylation of DUSP4 leads to its ubiquitination and degradation by HUWE1.
  • High p38 MAPK and PRMT1 levels correlate with thrombocytopenia and poor prognosis in MDS.
  • Inhibition of p38 MAPK or PRMT1 enhances megakaryopoiesis.

Conclusions:

  • The PRMT1-DUSP4-p38 axis is a key regulator of megakaryocyte differentiation.
  • Targeting this axis offers a potential therapeutic strategy for MDS-related thrombocytopenia.
Keywords:
DUSP4HUWE1MDSPRMT1leukemiamegakaryocytemyelodysplasia syndromep38platlettrombocytopenia

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