Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1-S transition

M. S. Song, S. J. Song, S. J. Kim, K. Nakayama, Keiichi Nakayama, D. S. Lim

研究成果: ジャーナルへの寄稿記事

43 引用 (Scopus)

抄録

The tumor suppressor RASSF1A is inactivated in many human cancers and is implicated in regulation of microtubule stability, cell cycle progression and apoptosis. However, the precise mechanisms of RASSF1A action and their regulation remain unclear. Here we show that Skp2, an oncogenic subunit of the Skp1-Cul1-F-box ubiquitin ligase complex, interacts with, ubiquitinates, and promotes the degradation of RASSF1A at the G1-S transition of the cell cycle. This Skp2-dependent destruction of RASSF1A requires phosphorylation of the latter on serine-203 by cyclin D-cyclin-dependent kinase 4. Interestingly, mutation of RASSF1A-phosphorylation site Ser203 to alanine results in a delay in cell cycle progression from G1 to S phase. Moreover, enforced expression of Skp2 abolishes the inhibitory effect of RASSF1A on cell proliferation. Finally, the delay in G1-S progression after Skp2 removal is normalized by depletion of RASSF1A. These findings suggest that the Skp2-mediated degradation of RASSF1A plays an important role in cell proliferation and survival.

元の言語英語
ページ(範囲)3176-3185
ページ数10
ジャーナルOncogene
27
発行部数22
DOI
出版物ステータス出版済み - 5 15 2008

Fingerprint

Ubiquitin
Cell Cycle
Phosphorylation
Cell Proliferation
Cyclin-Dependent Kinase 4
Cyclin D
Neoplasms
Ligases
S Phase
Microtubules
Alanine
Serine
Cell Survival
Apoptosis
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

これを引用

Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1-S transition. / Song, M. S.; Song, S. J.; Kim, S. J.; Nakayama, K.; Nakayama, Keiichi; Lim, D. S.

:: Oncogene, 巻 27, 番号 22, 15.05.2008, p. 3176-3185.

研究成果: ジャーナルへの寄稿記事

Song, M. S. ; Song, S. J. ; Kim, S. J. ; Nakayama, K. ; Nakayama, Keiichi ; Lim, D. S. / Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1-S transition. :: Oncogene. 2008 ; 巻 27, 番号 22. pp. 3176-3185.
@article{1ad1b4b3568840a08445e6bca1f165ed,
title = "Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1-S transition",
abstract = "The tumor suppressor RASSF1A is inactivated in many human cancers and is implicated in regulation of microtubule stability, cell cycle progression and apoptosis. However, the precise mechanisms of RASSF1A action and their regulation remain unclear. Here we show that Skp2, an oncogenic subunit of the Skp1-Cul1-F-box ubiquitin ligase complex, interacts with, ubiquitinates, and promotes the degradation of RASSF1A at the G1-S transition of the cell cycle. This Skp2-dependent destruction of RASSF1A requires phosphorylation of the latter on serine-203 by cyclin D-cyclin-dependent kinase 4. Interestingly, mutation of RASSF1A-phosphorylation site Ser203 to alanine results in a delay in cell cycle progression from G1 to S phase. Moreover, enforced expression of Skp2 abolishes the inhibitory effect of RASSF1A on cell proliferation. Finally, the delay in G1-S progression after Skp2 removal is normalized by depletion of RASSF1A. These findings suggest that the Skp2-mediated degradation of RASSF1A plays an important role in cell proliferation and survival.",
author = "Song, {M. S.} and Song, {S. J.} and Kim, {S. J.} and K. Nakayama and Keiichi Nakayama and Lim, {D. S.}",
year = "2008",
month = "5",
day = "15",
doi = "10.1038/sj.onc.1210971",
language = "English",
volume = "27",
pages = "3176--3185",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "22",

}

TY - JOUR

T1 - Skp2 regulates the antiproliferative function of the tumor suppressor RASSF1A via ubiquitin-mediated degradation at the G1-S transition

AU - Song, M. S.

AU - Song, S. J.

AU - Kim, S. J.

AU - Nakayama, K.

AU - Nakayama, Keiichi

AU - Lim, D. S.

PY - 2008/5/15

Y1 - 2008/5/15

N2 - The tumor suppressor RASSF1A is inactivated in many human cancers and is implicated in regulation of microtubule stability, cell cycle progression and apoptosis. However, the precise mechanisms of RASSF1A action and their regulation remain unclear. Here we show that Skp2, an oncogenic subunit of the Skp1-Cul1-F-box ubiquitin ligase complex, interacts with, ubiquitinates, and promotes the degradation of RASSF1A at the G1-S transition of the cell cycle. This Skp2-dependent destruction of RASSF1A requires phosphorylation of the latter on serine-203 by cyclin D-cyclin-dependent kinase 4. Interestingly, mutation of RASSF1A-phosphorylation site Ser203 to alanine results in a delay in cell cycle progression from G1 to S phase. Moreover, enforced expression of Skp2 abolishes the inhibitory effect of RASSF1A on cell proliferation. Finally, the delay in G1-S progression after Skp2 removal is normalized by depletion of RASSF1A. These findings suggest that the Skp2-mediated degradation of RASSF1A plays an important role in cell proliferation and survival.

AB - The tumor suppressor RASSF1A is inactivated in many human cancers and is implicated in regulation of microtubule stability, cell cycle progression and apoptosis. However, the precise mechanisms of RASSF1A action and their regulation remain unclear. Here we show that Skp2, an oncogenic subunit of the Skp1-Cul1-F-box ubiquitin ligase complex, interacts with, ubiquitinates, and promotes the degradation of RASSF1A at the G1-S transition of the cell cycle. This Skp2-dependent destruction of RASSF1A requires phosphorylation of the latter on serine-203 by cyclin D-cyclin-dependent kinase 4. Interestingly, mutation of RASSF1A-phosphorylation site Ser203 to alanine results in a delay in cell cycle progression from G1 to S phase. Moreover, enforced expression of Skp2 abolishes the inhibitory effect of RASSF1A on cell proliferation. Finally, the delay in G1-S progression after Skp2 removal is normalized by depletion of RASSF1A. These findings suggest that the Skp2-mediated degradation of RASSF1A plays an important role in cell proliferation and survival.

UR - http://www.scopus.com/inward/record.url?scp=43749089372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43749089372&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1210971

DO - 10.1038/sj.onc.1210971

M3 - Article

VL - 27

SP - 3176

EP - 3185

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 22

ER -