Language

English

Publication Date

1-23-2026

Journal

Life Science Alliance

DOI

10.26508/lsa.202503496

PMID

41577381

PMCID

PMC12830084

PubMedCentral® Posted Date

1-23-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Adult mammalian hearts exhibit limited regenerative capacity because of the restricted renewal of cardiomyocytes. Recent studies reveal that mammalian hearts exhibit transient regenerative potential within a short time frame after birth, suggesting a regulatory mechanism that prevents adult hearts from initiating a regenerative response to cardiac injury. Here, we discovered that an active form of YAP, named YAP6SA, which is not inhibited by the Hippo signaling pathway and does not interact with TEADs, induces cardiomyocyte cell cycle reentry. In addition, YAP6SA interacts with scaffold protein MPDZ to regulate Rho GTPases and promote cell cycle progression in cardiomyocytes (CMs). Importantly, YAP6SA overexpression is well tolerated in mammalian hearts. These findings provide new insights into YAP function in cardiomyocytes.

Keywords

Myocytes, Cardiac, Animals, Cell Cycle, YAP-Signaling Proteins, Mice, Signal Transduction, Adaptor Proteins, Signal Transducing, Transcription Factors, Cell Cycle Proteins, Humans, rho GTP-Binding Proteins, DNA-Binding Proteins, Hippo Signaling Pathway, Phosphoproteins, Regeneration, TEA Domain Transcription Factors

Published Open-Access

yes

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