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Basal Signaling Through Death Receptor 5 and Caspase 3 Activates p38 Kinase to Regulate Serum Response Factor – Mediated MyoD Transcription

Ross, Jason Allen
http://orcid.org/0000-0002-6140-0599
http://rave.ohiolink.edu/etdc/view?acc_num=csu160915772455676

Abstract Details

2020, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
The formation of functional skeletal muscle is the consequence of both the differentiation and apoptosis of skeletal myoblasts. Ex vivo culture of skeletal myoblasts provides a tractable model for the study of these two coordinately regulated processes. We have previously reported that 23A2 myoblasts stably expressing a dominant negative Death Receptor 5 (A2:dnDR5 myoblasts) exhibit decreased basal mRNA and protein expression of the master muscle regulatory transcription factor MyoD. This decrease at the mRNA level is not a consequence of altered stability. Binding of the transcription factor SRF to a non-canonical CArG box within a serum response element (SRE) in the distal regulatory region (DRR) of the MyoD gene is required for basal MyoD expression. Herein, we report that A2:dnDR5 myoblasts exhibit a decrease in the amount of SRF bound at this CArG box. Additionally, in A2:dnDR5 myoblasts, we observe a decrease in the phosphorylation indicative of activation of SRF as well as a decrease in the phosphorylation indicative of activation of the mitogen-activated protein kinase p38, which is known to activate SRF. Pharmacological inhibition of p38, or of caspase-3, in parental 23A2 myoblasts mimics the decreased activation of SRF and p38, the decreased binding of SRF to the MyoD CArG box, and the decreased levels of MyoD mRNA and protein detected in the A2:dnDR5 myoblasts. Taken together, these results suggest that basal signaling through DR5 to caspase 3 leads to the activation of p38 and subsequently SRF to maintain basal expression of MyoD.
Crystal Weyman (Advisor)
92 p.
Biology; Cellular Biology; Molecular Biology
MyoD; DR5; basal signaling; SRF; p38

Recommended Citations

Citations

  • Ross, J. A. (2020). Basal Signaling Through Death Receptor 5 and Caspase 3 Activates p38 Kinase to Regulate Serum Response Factor – Mediated MyoD Transcription [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu160915772455676

    APA Style (7th edition)

  • Ross, Jason. Basal Signaling Through Death Receptor 5 and Caspase 3 Activates p38 Kinase to Regulate Serum Response Factor – Mediated MyoD Transcription. 2020. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu160915772455676.

    MLA Style (8th edition)

  • Ross, Jason. "Basal Signaling Through Death Receptor 5 and Caspase 3 Activates p38 Kinase to Regulate Serum Response Factor – Mediated MyoD Transcription." Doctoral dissertation, Cleveland State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=csu160915772455676

    Chicago Manual of Style (17th edition)

csu160915772455676
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This open access ETD is published by Cleveland State University and OhioLINK.