PUBLICATION

A BMP4-p38 MAPK signaling axis controls ISL1 protein stability and activity during cardiogenesis

Authors
Jing, Y., Ren, Y., Witzel, H.R., Dobreva, G.
ID
ZDB-PUB-210731-7
Date
2021
Source
Stem Cell Reports   16(8): 1894-1905 (Journal)
Registered Authors
Dobreva, Gergana
Keywords
BMP signaling, ISL1, cardiac progenitor cells, cardiomyocyte differentiation, heart development, p38 MAPK, protein phosphorylation
MeSH Terms
  • p38 Mitogen-Activated Protein Kinases/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Animals, Genetically Modified
  • Stem Cells/metabolism
  • Organogenesis/genetics
  • Mice
  • Gene Expression Regulation, Developmental
  • Myocardium/cytology
  • Myocardium/metabolism*
  • Bone Morphogenetic Protein 4/metabolism*
  • NIH 3T3 Cells
  • Heart/embryology
  • Cell Differentiation/genetics
  • Mice, Knockout
  • LIM-Homeodomain Proteins/genetics
  • LIM-Homeodomain Proteins/metabolism*
  • Protein Stability
  • Signal Transduction*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Animals
(all 23)
PubMed
34329593 Full text @ Stem Cell Reports
Abstract
During development, cells respond rapidly to intra- and intercellular signals, which induce signaling cascades regulating the activity of transcription factors at the transcriptional and/or post-translational level. The transcription factor ISL1 plays a key role in second heart field development and cardiac differentiation, and its mRNA levels are tightly regulated during cardiogenesis. Here, we show that a BMP-p38 MAPK signaling axis controls ISL1 protein function at the post-translational level. BMP-mediated activation of p38 MAPK leads to ISL1 phosphorylation at S269 by p38, which prevents ISL1 degradation and ensures its transcriptional activity during cardiogenesis. Interfering with p38 MAPK signaling leads to the degradation of ISL1 by the proteasome, resulting in defects in cardiomyocyte differentiation and impaired zebrafish and mouse heart morphogenesis and function. Given the critical role of the tight control of ISL1 activity during cardiac lineage diversification, modulation of BMP4-p38 MAPK signaling could direct differentiation into specific cardiac cell subpopulations.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s883TgTransgenic Insertion
    sa29
      		Point Mutation
      uhm1
        		Small Deletion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        No data available
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
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        Mapping
        No data available
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        Citation
        Jing, Y., Ren, Y., Witzel, H.R., Dobreva, G. (2021) A BMP4-p38 MAPK signaling axis controls ISL1 protein stability and activity during cardiogenesis. Stem Cell Reports. 16(8):1894-1905.