Document Detail


Specific phosphorylation of SR proteins by mammalian DNA topoisomerase I.
MedLine Citation:
PMID:  8609994     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several metazoan splicing factors are characterized by ribonucleoprotein (RNP) consensus sequences and arginine-serine repeats (RS domain) which are essential for their function in splicing. These include members of the SR-protein family (SC35, SF2/ASF), the U1 small nuclear (sn) RNP protein (U1-70K) and the U2 snRNP auxiliary factor (U2AF). SR proteins are phosphorylated in vivo and the phosphorylation state of U1-70K's RS domain influences its splicing activity. Here we report the purification of a protein kinase that is specific for SR proteins and show that it is DNA topoisomerase I. This enzyme lacks a canonical ATP-binding motif but binds ATP with a dissociation constant of 50 nM. Camptothecin and derivatives, known to be specific inhibitors of DNA topoisomerase I, strongly inhibit the kinase activity in the presence of DNA and affect the phosphorylation state of SR proteins. Thus, DNA topoisomerase I may well be one of the SR protein kinases operating in vivo.
Authors:
F Rossi; E Labourier; T Forné; G Divita; J Derancourt; J F Riou; E Antoine; G Cathala; C Brunel; J Tazi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  381     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  1996 May 
Date Detail:
Created Date:  1996-05-30     Completed Date:  1996-05-30     Revised Date:  2011-09-27    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  80-2     Citation Subset:  IM    
Affiliation:
Institut de Génétique Moléculaire, Université de Montpellier II, France.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Camptothecin / analogs & derivatives,  pharmacology
Cell Line
DNA Topoisomerases, Type I / genetics,  metabolism*
Hela Cells
Humans
Nuclear Proteins / metabolism*
Phosphorylation / drug effects
Protein Kinases / metabolism*
Recombinant Proteins / metabolism
Topotecan
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/Recombinant Proteins; 123948-87-8/Topotecan; 170974-22-8/serine-arginine-rich splicing proteins; 56-65-5/Adenosine Triphosphate; 7689-03-4/Camptothecin; EC 2.7.-/Protein Kinases; EC 5.99.1.2/DNA Topoisomerases, Type I

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