Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing

Pheruza Tarapore, Kazuya Shinmura, Hitoshi Suzuki, Yukari Tokuyama, Song Hee Kim, Akira Maeda, Kenji Fukasawa

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 languageEnglish
Pages (from-to)399-409
Number of pages11
JournalFEBS Letters
Volume580
Issue number2
DOIs
Publication statusPublished - 23-01-2006

Fingerprint

Phosphorylation
RNA Precursors
Speckle
Processing
Cyclin A
Cyclin E
Centrosome
nucleophosmin
Phosphotransferases
Cyclin-Dependent Kinase 2
Casein Kinase II
Ribosomal RNA
Cyclin-Dependent Kinases
Phosphoproteins
Protein Transport
Ribosomes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Tarapore, Pheruza ; Shinmura, Kazuya ; Suzuki, Hitoshi ; Tokuyama, Yukari ; Kim, Song Hee ; Maeda, Akira ; Fukasawa, Kenji. / Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing. In: FEBS Letters. 2006 ; Vol. 580, No. 2. pp. 399-409.
@article{d36e52ea20104f2cb037db6052cc05e4,
title = "Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing",
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.",
author = "Pheruza Tarapore and Kazuya Shinmura and Hitoshi Suzuki and Yukari Tokuyama and Kim, {Song Hee} and Akira Maeda and Kenji Fukasawa",
year = "2006",
month = "1",
day = "23",
doi = "10.1016/j.febslet.2005.12.022",
language = "English",
volume = "580",
pages = "399--409",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "2",

}

Tarapore, P, Shinmura, K, Suzuki, H, Tokuyama, Y, Kim, SH, Maeda, A & Fukasawa, K 2006, 'Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing', FEBS Letters, vol. 580, no. 2, pp. 399-409. https://doi.org/10.1016/j.febslet.2005.12.022

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 journalArticle

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

VL - 580

SP - 399

EP - 409

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 2

ER -