PXD012040-2

PXD012040 is an original dataset announced via ProteomeXchange.

Title	VGLL3 Skeletal Muscle
Description	Vestigial-like (Vgll) proteins are transcriptional co-factors that have been reported to bind Tead family transcription factors to regulate various functions ranging from wing development in the fly to muscle fibre composition and immune function in mice. Here, we characterise Vgll3 in the skeletal muscle lineage. Vgll3 is expressed at low levels in unchallenging muscle but its expression increases in mechanically stimulated and regenerating muscle. VGLL3 is also >3-fold more expressed in the muscles of Duchenne muscular dystrophy patients than in healthy controls and VGLL3 expression is highest in PAX3-FOXO1-associated alveolar rhabdomyosarcoma when compared to other rhabdomyosarcomas, related tumours and adult muscle. Immunoprecipitation of over expressed VGLL3-flag followed by proteomics reveals that VGLL3 binds Tead1,3,4 transcription factors in myoblasts and myotubes. However, unlike Yap, there is no evidence for interaction with a regulatory system such as a kinase cascade. VGLL3 overexpression affects reduces the expression of members of the Hippo negative feedback loop and affects the expression of genes with important functions in muscle or signalling such as Myf5, Pitx2/3 as well as genes that encode Wnt members and IGF-binding proteins. It mainly represses gene expression and regulates similar genes as YAP1 S127A and TAZ S89A but not in a clear agonistic or antagonistic fashion. A loss of Vgll3 almost completely blocks the proliferation of human myoblasts and VGLL3 overexpression promotes myoblasts differentiation. In vivo, the loss of Vgll3 does not prevent normal skeletal muscle development presumably due to feedback signalling and/or redundancy. Collectively, this work identifies Vgll3 as a disease-related transcriptional co-factor that competes with the Hippo effectors Yap and Taz to control myoblast proliferation and differentiation.
HostingRepository	PRIDE
AnnounceDate	2020-01-20
AnnouncementXML	Submission_2020-01-20_00:41:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Matallanas
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-13 01:07:38	ID requested
1	2019-06-17 05:57:42	announced
⏵ 2	2020-01-20 00:41:39	announced	2020-01-20: Updated publication reference for PubMed record(s): 31138678.

Figeac N, Mohamed AD, Sun C, Sch, ö, nfelder M, Matallanas D, Garcia-Munoz A, Missiaglia E, Collie-Duguid E, De Mello V, Pobbati AV, Pruller J, Jaka O, Harridge SDR, Hong W, Shipley J, Vargesson N, Zammit PS, Wackerhage H, VGLL3 operates via TEAD1, TEAD3 and TEAD4 to influence myogenesis in skeletal muscle. J Cell Sci, 132(13):(2019) [pubmed]

curator keyword: Biological

submitter keyword: Human, VGLL3, IP, Immunoprecipitation

David Matallanas
contact affiliation	Systems Biology Ireland, University College Dublin
contact email	david.gomez@ucd.ie
lab head
David Matallanas
contact affiliation	Systems Biology Ireland, University College Dublin
contact email	david.gomez@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012040
     1. Label: PRIDE project
     2. Name: VGLL3 Skeletal Muscle