Reciprocal Regulation of PPARγ and RUNX2 Activities in Marrow Mesenchymal Stem Cells: Fine Balance between p38 MAPK and Protein Phosphatase 5
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Purpose of Review
Post-translational modifications (PTMs), specifically serine phosphorylation, are essential for determination and tuning up an activity of many proteins, including those that are involved in the control of gene transcription. Transcription factors PPARγ2 and RUNX2 are essential for mesenchymal stem cell (MSC) commitment to either adipocyte or osteoblast lineage. This review is summarizing current knowledge how serine phosphorylation PTMs regulate activities of both transcription factors and MSCs lineage commitment.
Both PPARγ2 and RUNX2 transcriptional activities are regulated by similar PTMs, however with an opposite outcome. The same p38 MAPK mediates serine phosphorylation that leads to activation of RUNX2 and inactivation of PPARγ2. The process of protein phosphorylation is balanced with a process of protein dephosphorylation. Protein phosphatase 5 simultaneously dephosphorylates both proteins, which results in activation of PPARγ2 and inactivation of RUNX2.
This review provides a summary of the “yin yang” fine-tuned mechanism by which p38 MAPK and PP5 regulate MSCs lineage commitment.
KeywordsOsteoblasts Adipocytes p38 MAPK PP5 RUNX2 PPARγ2 Bone Rosiglitazone
This work was supported by the American Diabetes Association (ADA) grant no.1-17-PDF-067 to LAS and grants from NIH DK105825 and ADA 7-13-BS-089 to BLC.
Compliance with Ethical Standards
Conflict of Interest
Lance A. Stechschulte and Beata Lecka-Czernik declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of major importance
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