The kinase domain of titin controls muscle gene expression and protein turnover

Stephan Lange, Fengqing Xiang, Andrey Yakovenko, Anna Vihola, Peter Hackman, Elena Rostkova, Jakob Kristensen, Birgit Brandmeier, Gereon Franzen, Birgitta Hedberg, Lars Gunnar Gunnarsson, Simon M Hughes, Sylvie Marchand, Thomas Sejersen, Isabelle Richard, Lars Edström, Elisabeth Ehler, Bjarne Udd, Mathias Gautel

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

The giant sarcomeric protein titin contains a protein kinase domain (TK) ideally positioned to sense mechanical load. We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation. Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor (SRF). Nuclear translocation of MuRF2 was induced by mechanical inactivity and caused reduction of nuclear SRF and repression of transcription. A human mutation in the titin,protein kinase domain causes hereditary muscle disease by disrupting this pathway.
Alkuperäiskielienglanti
LehtiScience
Vuosikerta308
Numero5728
Sivut1599-1603
Sivumäärä5
ISSN0036-8075
DOI - pysyväislinkit
TilaJulkaistu - 2005
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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