A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors

Gustavo A. Miranda-Carboni, Susan A. Krum, Kathleen Yee, Miguel Nava, Qiming E. Deng, Shehla Pervin, Alicia Collado-Hidalgo, Zoran Galić, Jerome A. Zack, Keiko Nakayama, Keiichi I. Nakayama, Timothy F. Lane

研究成果: ジャーナルへの寄稿記事

59 引用 (Scopus)

抄録

Loss of the CDK inhibitor p27KIP1 is widely linked with poor prognosis in human cancer. In Wnt10b-expressing mammary tumors, levels of p27KIP1 were extremely low; conversely, Wnt10b-null mammary cells expressed high levels of this protein, suggesting Wnt-dependent regulation of p27KIP1. Interestingly we found that Wnt-induced turnover of p27 KIP1 was independent from classical SCFSKP2-mediated degradation in both mouse and human cells. Instead, turnover required Cullin 4A and Cullin 4B, components of an alternative E3 ubiquitin ligase induced in response to active Wnt signaling. We found that CUL4A was a novel Wnt target gene in both mouse and human cells and that CUL4A physically interacted with p27KIP1 in Wnt-responding cells. We further demonstrated that both Cul4A and Cul4B were required for Wnt-induced p27KIP1 degradation and S-phase progression. CUL4A and CUL4B are therefore components of a conserved Wnt-induced proteasome targeting (WIPT) complex that regulates p27 KIP1 levels and cell cycle progression in mammalian cells.

元の言語英語
ページ(範囲)3121-3134
ページ数14
ジャーナルGenes and Development
22
発行部数22
DOI
出版物ステータス出版済み - 11 15 2008

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Cullin Proteins
Breast Neoplasms
Wnt Proteins
Null Lymphocytes
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
S Phase
Cell Cycle
Breast
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

これを引用

Miranda-Carboni, G. A., Krum, S. A., Yee, K., Nava, M., Deng, Q. E., Pervin, S., ... Lane, T. F. (2008). A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors. Genes and Development, 22(22), 3121-3134. https://doi.org/10.1101/gad.1692808

A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors. / Miranda-Carboni, Gustavo A.; Krum, Susan A.; Yee, Kathleen; Nava, Miguel; Deng, Qiming E.; Pervin, Shehla; Collado-Hidalgo, Alicia; Galić, Zoran; Zack, Jerome A.; Nakayama, Keiko; Nakayama, Keiichi I.; Lane, Timothy F.

:: Genes and Development, 巻 22, 番号 22, 15.11.2008, p. 3121-3134.

研究成果: ジャーナルへの寄稿記事

Miranda-Carboni, GA, Krum, SA, Yee, K, Nava, M, Deng, QE, Pervin, S, Collado-Hidalgo, A, Galić, Z, Zack, JA, Nakayama, K, Nakayama, KI & Lane, TF 2008, 'A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors', Genes and Development, 巻. 22, 番号 22, pp. 3121-3134. https://doi.org/10.1101/gad.1692808
Miranda-Carboni GA, Krum SA, Yee K, Nava M, Deng QE, Pervin S その他. A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors. Genes and Development. 2008 11 15;22(22):3121-3134. https://doi.org/10.1101/gad.1692808
Miranda-Carboni, Gustavo A. ; Krum, Susan A. ; Yee, Kathleen ; Nava, Miguel ; Deng, Qiming E. ; Pervin, Shehla ; Collado-Hidalgo, Alicia ; Galić, Zoran ; Zack, Jerome A. ; Nakayama, Keiko ; Nakayama, Keiichi I. ; Lane, Timothy F. / A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors. :: Genes and Development. 2008 ; 巻 22, 番号 22. pp. 3121-3134.
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