Publikationsdatum:
2005-04-02
Beschreibung:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lange, Stephan -- Xiang, Fengqing -- Yakovenko, Andrey -- Vihola, Anna -- Hackman, Peter -- Rostkova, Elena -- Kristensen, Jakob -- Brandmeier, Birgit -- Franzen, Gereon -- Hedberg, Birgitta -- Gunnarsson, Lars Gunnar -- Hughes, Simon M -- Marchand, Sylvie -- Sejersen, Thomas -- Richard, Isabelle -- Edstrom, Lars -- Ehler, Elisabeth -- Udd, Bjarne -- Gautel, Mathias -- G0200496(63216)/Medical Research Council/United Kingdom -- G0300213/Medical Research Council/United Kingdom -- PG/03/049/15364/British Heart Foundation/United Kingdom -- New York, N.Y. -- Science. 2005 Jun 10;308(5728):1599-603. Epub 2005 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Muscle Signalling and Development, Randall Division, King's College London, London SE1 1UL, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15802564" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Amino Acid Sequence
;
Amino Acid Substitution
;
Animals
;
Catalytic Domain
;
Cell Line
;
Cell Nucleus/metabolism
;
Connectin
;
*Gene Expression Regulation
;
Heat-Shock Proteins/metabolism
;
Humans
;
Ligands
;
Mice
;
Mice, Inbred C3H
;
Molecular Sequence Data
;
Muscle Proteins/*chemistry/genetics/*metabolism
;
Muscle, Skeletal/*metabolism
;
Muscular Diseases/genetics
;
Mutation
;
Myocytes, Cardiac/*metabolism
;
Protein Binding
;
Protein Conformation
;
Protein Kinases/*chemistry/genetics/*metabolism
;
Protein Structure, Tertiary
;
Proteins/metabolism
;
Rats
;
Respiratory Insufficiency/genetics/metabolism
;
Sarcomeres/metabolism
;
Serum Response Factor/metabolism
;
Signal Transduction
;
Two-Hybrid System Techniques
;
Ubiquitin-Protein Ligases/metabolism
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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