Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-20
pubmed:abstractText
Nucleophosmin (NPM) is a multifunctional phosphoprotein, being involved in ribosome assembly, pre-ribosomal RNA processing, DNA duplication, nucleocytoplasmic protein trafficking, and centrosome duplication. NPM is phosphorylated by several kinases, including nuclear kinase II, casein kinase 2, Polo-like kinase 1 and cyclin-dependent kinases (CDK1 and 2), and these phosphorylations modulate the activity and function of NPM. We have previously identified Thr(199) as the major phosphorylation site of NPM mediated by CDK2/cyclin E (and A), and this phosphorylation is involved in the regulation of centrosome duplication. In this study, we further examined the effect of CDK2-mediated phosphorylation of NPM by using the antibody that specifically recognizes NPM phosphorylated on Thr(199). We found that the phospho-Thr(199) NPM localized to dynamic sub-nuclear structures known as nuclear speckles, which are believed to be the sites of storage and/or assembly of pre-mRNA splicing factors. Phosphorylation on Thr(199) by CDK2/cyclin E (and A) targets NPM to nuclear speckles, and enhances the RNA-binding activity of NPM. Moreover, phospho-Thr(199) NPM, but not unphosphorylated NPM, effectively represses pre-mRNA splicing. These findings indicate the involvement of NPM in the regulation of pre-mRNA processing, and its activity is controlled by CDK2-mediated phosphorylation on Thr(199).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-5793
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
580
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
399-409
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16376875-Animals, pubmed-meshheading:16376875-Antibodies, Phospho-Specific, pubmed-meshheading:16376875-Cell Nucleus, pubmed-meshheading:16376875-Cells, Cultured, pubmed-meshheading:16376875-Cyclin A, pubmed-meshheading:16376875-Cyclin E, pubmed-meshheading:16376875-Cyclin-Dependent Kinase 2, pubmed-meshheading:16376875-Fibroblasts, pubmed-meshheading:16376875-Humans, pubmed-meshheading:16376875-Mice, pubmed-meshheading:16376875-Mice, Inbred C57BL, pubmed-meshheading:16376875-Nuclear Proteins, pubmed-meshheading:16376875-Phosphorylation, pubmed-meshheading:16376875-RNA, Messenger, pubmed-meshheading:16376875-RNA Precursors, pubmed-meshheading:16376875-RNA Processing, Post-Transcriptional, pubmed-meshheading:16376875-RNA-Binding Proteins, pubmed-meshheading:16376875-Recombinant Fusion Proteins, pubmed-meshheading:16376875-Threonine
pubmed:year
2006
pubmed:articleTitle
Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing.
pubmed:affiliation
Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0521, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural