Interaction of YAP with the Myb-MuvB (MMB) complex defines a transcriptional program to promote the proliferation of cardiomyocytes


Autoři: Marco Gründl aff001;  Susanne Walz aff002;  Laura Hauf aff001;  Melissa Schwab aff001;  Kerstin Marcela Werner aff001;  Susanne Spahr aff001;  Clemens Schulte aff003;  Hans Michael Maric aff003;  Carsten P. Ade aff001;  Stefan Gaubatz aff001
Působiště autorů: Theodor Boveri Institute and Comprehensive Cancer Center Mainfranken, Biocenter University of Wuerzburg, Wuerzburg, Germany aff001;  Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Wuerzburg, Wuerzburg, Germany aff002;  Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Wuerzburg, Germany aff003
Vyšlo v časopise: Interaction of YAP with the Myb-MuvB (MMB) complex defines a transcriptional program to promote the proliferation of cardiomyocytes. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008818
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008818

Souhrn

The Hippo signalling pathway and its central effector YAP regulate proliferation of cardiomyocytes and growth of the heart. Using genetic models in mice we show that the increased proliferation of embryonal and postnatal cardiomyocytes due to loss of the Hippo-signaling component SAV1 depends on the Myb-MuvB (MMB) complex. Similarly, proliferation of postnatal cardiomyocytes induced by constitutive active YAP requires MMB. Genome studies revealed that YAP and MMB regulate an overlapping set of cell cycle genes in cardiomyocytes. Protein-protein interaction studies in cell lines and with recombinant proteins showed that YAP binds directly to B-MYB, a subunit of MMB, in a manner dependent on the YAP WW domains and a PPXY motif in B-MYB. Disruption of the interaction by overexpression of the YAP binding domain of B-MYB strongly inhibits the proliferation of cardiomyocytes. Our results point to MMB as a critical downstream effector of YAP in the control of cardiomyocyte proliferation.

Klíčová slova:

Cardiac ventricles – Cardiomyocytes – Cell cycle and cell division – Gene expression – Heart – Immunoblotting – Immunoprecipitation – Mitosis


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Štítky
Genetika Reprodukční medicína

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PLOS Genetics


2020 Číslo 5

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