CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during s phase and after UV irradiation

Hideo Nishitani, Yasushi Shiomi, Hiroka Iida, Masato Michishita, Toshihiro Takami, Toshiki Tsurimoto

研究成果: ジャーナルへの寄稿記事

179 引用 (Scopus)

抄録

Previous reports showed that chromatin-associated PCNA couples DNA replication with Cul4-DDB1Cdt2-dependent proteolysis of the licensing factor Cdt1. The CDK inhibitor p21, another PCNA-binding protein, is also degraded both in S phase and after UV irradiation. Here we show that p21 is degraded by the same ubiquitin-proteasome pathway as Cdt1 in HeLa cells. When PCNA or components of Cul4-DDB1Cdt2 were silenced or when the PCNA binding site on p21 was mutated, degradation of p21 was prevented both in S phase and after UV irradiation. p21 was co- immunoprecipitated with Cul4A and DDB1 proteins when expressed in cells. The purified Cul4A-DDB1Cdt2 complex ubiquitinated p21 in vitro. Consistently, p21 protein levels are low during S phase and increase around G2 phase. Mutational analysis suggested that in addition to the PCNA binding domain, its flanking regions are also important for recognition by Cul4-DDB1Cdt2. Our findings provide a new aspect of proteolytic control of p21 during the cell cycle.

元の言語英語
ページ(範囲)29045-29052
ページ数8
ジャーナルJournal of Biological Chemistry
283
発行部数43
DOI
出版物ステータス出版済み - 10 24 2008

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Proliferating Cell Nuclear Antigen
Irradiation
S Phase
Proteolysis
G2 Phase
Proteasome Endopeptidase Complex
Licensure
Ubiquitin
DNA Replication
HeLa Cells
Chromatin
Cell Cycle
Carrier Proteins
Proteins
Binding Sites
Cells
Degradation
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during s phase and after UV irradiation. / Nishitani, Hideo; Shiomi, Yasushi; Iida, Hiroka; Michishita, Masato; Takami, Toshihiro; Tsurimoto, Toshiki.

:: Journal of Biological Chemistry, 巻 283, 番号 43, 24.10.2008, p. 29045-29052.

研究成果: ジャーナルへの寄稿記事

Nishitani, Hideo ; Shiomi, Yasushi ; Iida, Hiroka ; Michishita, Masato ; Takami, Toshihiro ; Tsurimoto, Toshiki. / CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during s phase and after UV irradiation. :: Journal of Biological Chemistry. 2008 ; 巻 283, 番号 43. pp. 29045-29052.
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abstract = "Previous reports showed that chromatin-associated PCNA couples DNA replication with Cul4-DDB1Cdt2-dependent proteolysis of the licensing factor Cdt1. The CDK inhibitor p21, another PCNA-binding protein, is also degraded both in S phase and after UV irradiation. Here we show that p21 is degraded by the same ubiquitin-proteasome pathway as Cdt1 in HeLa cells. When PCNA or components of Cul4-DDB1Cdt2 were silenced or when the PCNA binding site on p21 was mutated, degradation of p21 was prevented both in S phase and after UV irradiation. p21 was co- immunoprecipitated with Cul4A and DDB1 proteins when expressed in cells. The purified Cul4A-DDB1Cdt2 complex ubiquitinated p21 in vitro. Consistently, p21 protein levels are low during S phase and increase around G2 phase. Mutational analysis suggested that in addition to the PCNA binding domain, its flanking regions are also important for recognition by Cul4-DDB1Cdt2. Our findings provide a new aspect of proteolytic control of p21 during the cell cycle.",
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AU - Shiomi, Yasushi

AU - Iida, Hiroka

AU - Michishita, Masato

AU - Takami, Toshihiro

AU - Tsurimoto, Toshiki

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