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The multifunctional nuclear protein p54nrb is multiphosphorylated in mitosis and interacts with the mitotic regulator Pin1.
- Source :
-
Journal of molecular biology [J Mol Biol] 2005 Mar 04; Vol. 346 (4), pp. 1163-72. Date of Electronic Publication: 2005 Jan 12. - Publication Year :
- 2005
-
Abstract
- The human protein p54nrb and its mouse homolog NonO have been implicated in a variety of nuclear processes including transcription, pre-mRNA processing, nuclear retention of edited RNA and DNA relaxation. We have identified p54nrb as an antigen of the phosphodependent monoclonal antibodies CC-3 and MPM-2 and shown that this protein is phosphorylated on multiple sites during mitosis. The use of the cyclin-dependent protein kinase inhibitor roscovitine and immunodepletion studies with an anti-cyclin B1 antibody established that Cdk1 was responsible for the phosphorylation of the carboxy-terminal extremity of p54nrb whereas a different kinase appeared to be involved in the generation of CC-3 epitope(s) in the amino-terminal moiety of the protein. Like many CC-3 and MPM-2 antigens, we show that p54nrb is a target of the peptidylprolyl isomerase Pin1, suggesting that it may be regulated by phosphorylation-dependent conformational changes as many other nuclear proteins upon entry into mitosis. In addition, site-directed mutagenesis indicated that the interaction of Pin1 with p54nrb was mediated by three threonine residues located in the proline-rich carboxy-terminal extremity of the protein. Our results also showed that Pin1 binding was favored when at least two of the three threonine residues were phosphorylated, suggesting a regulation mechanism based on multisite phosphorylation.
- Subjects :
- Animals
CDC2 Protein Kinase metabolism
Epitopes immunology
HeLa Cells
Humans
Mice
NIMA-Interacting Peptidylprolyl Isomerase
Nuclear Matrix-Associated Proteins genetics
Nuclear Proteins genetics
Phosphorylation
Protein Binding
Protein Serine-Threonine Kinases immunology
Protein Serine-Threonine Kinases metabolism
RNA-Binding Proteins genetics
Substrate Specificity
Mitosis
Nuclear Matrix-Associated Proteins metabolism
Nuclear Proteins metabolism
Peptidylprolyl Isomerase metabolism
RNA-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2836
- Volume :
- 346
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 15701524
- Full Text :
- https://doi.org/10.1016/j.jmb.2004.12.034