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Publication : Dual function of VGLL4 in muscle regeneration.

First Author  Feng X Year  2019
Journal  EMBO J Volume  38
Issue  17 Pages  e101051
PubMed ID  31328806 Mgi Jnum  J:280923
Mgi Id  MGI:6370298 Doi  10.15252/embj.2018101051
Citation  Feng X, et al. (2019) Dual function of VGLL4 in muscle regeneration. EMBO J 38(17):e101051
abstractText  VGLL4 has previously been identified as a negative regulator of YAP. Here we show that VGLL4 regulates muscle regeneration in both YAP-dependent and YAP-independent manners at different stages. Knockout of VGLL4 in mice leads to smaller myofiber size and defective muscle contraction force. Furthermore, our studies reveal that knockout of VGLL4 results in increased muscle satellite cells proliferation and impaired myoblast differentiation, which ultimately leads to delayed muscle regeneration. Mechanistically, the results show that VGLL4 works as a conventional repressor of YAP at the proliferation stage of muscle regeneration. At the differentiation stage, VGLL4 acts as a co-activator of TEAD4 to promote MyoG transactivation and facilitate the initiation of differentiation in a YAP-independent manner. Moreover, VGLL4 stabilizes the protein-protein interactions between MyoD and TEAD4 to achieve efficient MyoG transactivation. Our findings define the dual roles of VGLL4 in regulating muscle regeneration at different stages and may open novel therapeutic perspectives for muscle regeneration.
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