Deregulated Proteolysis of the Cell Cycle Regulator p27Kip1 and Cancers

Etsuo Susaki, Keiichi Nakayama

研究成果: ジャーナルへの寄稿評論記事

抄録

Reduced expression of p27, a member of CDK inhibitors, is observed in a variety of human cancers, and many studies have indicated that downregulation of the p27 expression correlates with poor prognosis. p27 acts as a negative regulator of the cell cycle, and its degradation by the ubiquitin-proteasome pathway is a critical event for the cell cycle progression to S phase. The degradation of p27 is regulated by phosphorylations prior to ubiquitination that is mediated by the SCFSkp2 ubiquitin ligase complex. The low levels of p27 protein in many cancer cells seem attributable to enhanced proteolysis. In fact, increased levels of Skp2 protein are found in many tumors, and the overexpression of Skp2 may also be related to the high grade of cancers. Previous reports have suggested that p27 is clinically useful as an independent prognostic marker for cancer patients, and trials of new treatments targeting p27 have already started. p27 is also implicated to play a role in other cell functions, such as cell differentiation, apoptosis, and cell-cell adhesion. Thus, a variety of mechanisms seem to underlie the deregulation of p27 in cancer cells, which remain to be elucidated.

元の言語英語
ページ(範囲)546-555
ページ数10
ジャーナルBiotherapy
17
発行部数6
出版物ステータス出版済み - 11 2003

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Proteolysis
Cell Cycle
Neoplasms
Ubiquitin
S-Phase Kinase-Associated Proteins
Ubiquitination
Proteasome Endopeptidase Complex
Ligases
S Phase
Cell Adhesion
Cell Differentiation
Down-Regulation
Phosphorylation
Apoptosis
Proteins

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Immunology and Allergy

これを引用

Deregulated Proteolysis of the Cell Cycle Regulator p27Kip1 and Cancers. / Susaki, Etsuo; Nakayama, Keiichi.

:: Biotherapy, 巻 17, 番号 6, 11.2003, p. 546-555.

研究成果: ジャーナルへの寄稿評論記事

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abstract = "Reduced expression of p27, a member of CDK inhibitors, is observed in a variety of human cancers, and many studies have indicated that downregulation of the p27 expression correlates with poor prognosis. p27 acts as a negative regulator of the cell cycle, and its degradation by the ubiquitin-proteasome pathway is a critical event for the cell cycle progression to S phase. The degradation of p27 is regulated by phosphorylations prior to ubiquitination that is mediated by the SCFSkp2 ubiquitin ligase complex. The low levels of p27 protein in many cancer cells seem attributable to enhanced proteolysis. In fact, increased levels of Skp2 protein are found in many tumors, and the overexpression of Skp2 may also be related to the high grade of cancers. Previous reports have suggested that p27 is clinically useful as an independent prognostic marker for cancer patients, and trials of new treatments targeting p27 have already started. p27 is also implicated to play a role in other cell functions, such as cell differentiation, apoptosis, and cell-cell adhesion. Thus, a variety of mechanisms seem to underlie the deregulation of p27 in cancer cells, which remain to be elucidated.",
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