MHI Seminar Series presents Zhong Wang, Ph.D., Associate Professor, Cardiac Surgery, University of Michigan, Ann Arbor, MI

Summary of Seminar:  Cell fate conversion is associated with extensive epigenetic and post-translational modifications (PTMs) and architectural changes of sub-organelles and organelles; yet, how these events are interconnected remains unknown. I will discuss our identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and epigenetic factors. Akt1 kinase and PP2A phosphatase are a key writer and eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3 embedded factors, such as Hdac4, Mef2c, Nrip1, and Foxo1, form Hdac4 organized inhibitory nuclear condensates. Notably, PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a post-translational modification code can be a general mechanism for stimulating cell reprogramming and organ regeneration.

UNC Lineberger Comprehensive Cancer Center, Pagano Conference Room (LCCC 00-002)
450 West Dr.
Chapel HIll, North Carolina 27599
United States
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