Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export

Noriko Ishida, Taichi Hara, Takumi Kamura, Minoru Yoshida, Keiko Nakayama, Keiichi I. Nakayama

Research output: Contribution to journalArticle

228 Citations (Scopus)

Abstract

Phosphorylation of the cyclin-dependent kinase inhibitor p27Kip1 has been thought to regulate its stability. Ser10 is the major phosphorylation site of p27Kip1, and phosphorylation of this residue affects protein stability. Phosphorylation of p27Kip1 on Ser10 has now been shown to be required for the binding of CRM1, a carrier protein for nuclear export. The p27Kip1 protein was translocated from the nucleus to the cytoplasm at the G0-G1 transition of the cell cycle, and this export was inhibited by leptomycin B, a specific inhibitor of CRM1-dependent nuclear export. The nuclear export and subsequent degradation of p27Kip at the G0-G1 transition were observed in cells lacking Skp2, the F-box protein component of an SCF ubiquitin ligase complex, indicating that these early events are independent of Skp2-mediated proteolysis. Substitution of Ser10 with Ala (S10A) markedly reduced the extent of p27Kip1 export, whereas substitution of Ser10 with Asp (S10D) or Glu (S10E) promoted export. Co-immunoprecipitation analysis showed that CRM1 preferentially interacted with S10D and S10E but not with S10A, suggesting that the phosphorylation of p27Kip1 on Ser10 is required for its binding to CRM1 and for its subsequent nuclear export.

Original languageEnglish
Pages (from-to)14355-14358
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number17
DOIs
Publication statusPublished - 2002 Apr 26
Externally publishedYes

Fingerprint

Phosphorylation
Cell Nucleus Active Transport
Serine
SKP Cullin F-Box Protein Ligases
Substitution reactions
F-Box Proteins
Cyclin-Dependent Kinase Inhibitor p27
Proteolysis
Cyclin-Dependent Kinases
Protein Stability
Viperidae
Immunoprecipitation
Cell Cycle
Carrier Proteins
Cytoplasm
Cells
Degradation
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export. / Ishida, Noriko; Hara, Taichi; Kamura, Takumi; Yoshida, Minoru; Nakayama, Keiko; Nakayama, Keiichi I.

In: Journal of Biological Chemistry, Vol. 277, No. 17, 26.04.2002, p. 14355-14358.

Research output: Contribution to journalArticle

Ishida, Noriko ; Hara, Taichi ; Kamura, Takumi ; Yoshida, Minoru ; Nakayama, Keiko ; Nakayama, Keiichi I. / Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 17. pp. 14355-14358.
@article{19f19cdab7104099983f3d9195a5138d,
title = "Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export",
abstract = "Phosphorylation of the cyclin-dependent kinase inhibitor p27Kip1 has been thought to regulate its stability. Ser10 is the major phosphorylation site of p27Kip1, and phosphorylation of this residue affects protein stability. Phosphorylation of p27Kip1 on Ser10 has now been shown to be required for the binding of CRM1, a carrier protein for nuclear export. The p27Kip1 protein was translocated from the nucleus to the cytoplasm at the G0-G1 transition of the cell cycle, and this export was inhibited by leptomycin B, a specific inhibitor of CRM1-dependent nuclear export. The nuclear export and subsequent degradation of p27Kip at the G0-G1 transition were observed in cells lacking Skp2, the F-box protein component of an SCF ubiquitin ligase complex, indicating that these early events are independent of Skp2-mediated proteolysis. Substitution of Ser10 with Ala (S10A) markedly reduced the extent of p27Kip1 export, whereas substitution of Ser10 with Asp (S10D) or Glu (S10E) promoted export. Co-immunoprecipitation analysis showed that CRM1 preferentially interacted with S10D and S10E but not with S10A, suggesting that the phosphorylation of p27Kip1 on Ser10 is required for its binding to CRM1 and for its subsequent nuclear export.",
author = "Noriko Ishida and Taichi Hara and Takumi Kamura and Minoru Yoshida and Keiko Nakayama and Nakayama, {Keiichi I.}",
year = "2002",
month = "4",
day = "26",
doi = "10.1074/jbc.C100762200",
language = "English",
volume = "277",
pages = "14355--14358",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "17",

}

TY - JOUR

T1 - Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export

AU - Ishida, Noriko

AU - Hara, Taichi

AU - Kamura, Takumi

AU - Yoshida, Minoru

AU - Nakayama, Keiko

AU - Nakayama, Keiichi I.

PY - 2002/4/26

Y1 - 2002/4/26

N2 - Phosphorylation of the cyclin-dependent kinase inhibitor p27Kip1 has been thought to regulate its stability. Ser10 is the major phosphorylation site of p27Kip1, and phosphorylation of this residue affects protein stability. Phosphorylation of p27Kip1 on Ser10 has now been shown to be required for the binding of CRM1, a carrier protein for nuclear export. The p27Kip1 protein was translocated from the nucleus to the cytoplasm at the G0-G1 transition of the cell cycle, and this export was inhibited by leptomycin B, a specific inhibitor of CRM1-dependent nuclear export. The nuclear export and subsequent degradation of p27Kip at the G0-G1 transition were observed in cells lacking Skp2, the F-box protein component of an SCF ubiquitin ligase complex, indicating that these early events are independent of Skp2-mediated proteolysis. Substitution of Ser10 with Ala (S10A) markedly reduced the extent of p27Kip1 export, whereas substitution of Ser10 with Asp (S10D) or Glu (S10E) promoted export. Co-immunoprecipitation analysis showed that CRM1 preferentially interacted with S10D and S10E but not with S10A, suggesting that the phosphorylation of p27Kip1 on Ser10 is required for its binding to CRM1 and for its subsequent nuclear export.

AB - Phosphorylation of the cyclin-dependent kinase inhibitor p27Kip1 has been thought to regulate its stability. Ser10 is the major phosphorylation site of p27Kip1, and phosphorylation of this residue affects protein stability. Phosphorylation of p27Kip1 on Ser10 has now been shown to be required for the binding of CRM1, a carrier protein for nuclear export. The p27Kip1 protein was translocated from the nucleus to the cytoplasm at the G0-G1 transition of the cell cycle, and this export was inhibited by leptomycin B, a specific inhibitor of CRM1-dependent nuclear export. The nuclear export and subsequent degradation of p27Kip at the G0-G1 transition were observed in cells lacking Skp2, the F-box protein component of an SCF ubiquitin ligase complex, indicating that these early events are independent of Skp2-mediated proteolysis. Substitution of Ser10 with Ala (S10A) markedly reduced the extent of p27Kip1 export, whereas substitution of Ser10 with Asp (S10D) or Glu (S10E) promoted export. Co-immunoprecipitation analysis showed that CRM1 preferentially interacted with S10D and S10E but not with S10A, suggesting that the phosphorylation of p27Kip1 on Ser10 is required for its binding to CRM1 and for its subsequent nuclear export.

UR - http://www.scopus.com/inward/record.url?scp=0037177386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037177386&partnerID=8YFLogxK

U2 - 10.1074/jbc.C100762200

DO - 10.1074/jbc.C100762200

M3 - Article

VL - 277

SP - 14355

EP - 14358

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 17

ER -