Abstract
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 Thr199 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 Thr199. We found that the phospho-Thr199 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 Thr199 by CDK2/cyclin E (and A) targets NPM to nuclear speckles, and enhances the RNA-binding activity of NPM. Moreover, phospho-Thr199 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.
| Original language | English |
|---|---|
| Pages (from-to) | 399-409 |
| Number of pages | 11 |
| Journal | FEBS Letters |
| Volume | 580 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 23-01-2006 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology
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Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing. / Tarapore, Pheruza; Shinmura, Kazuya; Suzuki, Hitoshi; Tokuyama, Yukari; Kim, Song Hee; Maeda, Akira; Fukasawa, Kenji.
In: FEBS Letters, Vol. 580, No. 2, 23.01.2006, p. 399-409.Research output: Contribution to journal › Article
TY - JOUR
T1 - Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing
AU - Tarapore, Pheruza
AU - Shinmura, Kazuya
AU - Suzuki, Hitoshi
AU - Tokuyama, Yukari
AU - Kim, Song Hee
AU - Maeda, Akira
AU - Fukasawa, Kenji
PY - 2006/1/23
Y1 - 2006/1/23
N2 - 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 Thr199 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 Thr199. We found that the phospho-Thr199 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 Thr199 by CDK2/cyclin E (and A) targets NPM to nuclear speckles, and enhances the RNA-binding activity of NPM. Moreover, phospho-Thr199 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.
AB - 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 Thr199 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 Thr199. We found that the phospho-Thr199 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 Thr199 by CDK2/cyclin E (and A) targets NPM to nuclear speckles, and enhances the RNA-binding activity of NPM. Moreover, phospho-Thr199 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.
UR - http://www.scopus.com/inward/record.url?scp=30644477949&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30644477949&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2005.12.022
DO - 10.1016/j.febslet.2005.12.022
M3 - Article
C2 - 16376875
AN - SCOPUS:30644477949
VL - 580
SP - 399
EP - 409
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 2
ER -