UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53

Hong Wu, Scott L. Pomeroy, Manuel Ferreira, Natalia Teider, Juliana Mariani, Keiichi I. Nakayama, Shigetsugu Hatakeyama, Victor A. Tron, Linda F. Saltibus, Leo Spyracopoulos, Roger P. Leng

研究成果: ジャーナルへの寄稿記事

61 引用 (Scopus)

抄録

The TP53 gene (encoding the p53 tumor suppressor) is rarely mutated, although frequently inactivated, in medulloblastoma and ependymoma. Recent work in mouse models showed that the loss of p53 accelerated the development of medulloblastoma. The mechanism underlying p53 inactivation in human brain tumors is not completely understood. We show that ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice). UBE4B promotes p53 polyubiquitination and degradation and inhibits p53-dependent transactivation and apoptosis. Notably, silencing UBE4B expression impairs xenotransplanted tumor growth in a p53-dependent manner and overexpression of UBE4B correlates with decreased expression of p53 in these tumors. We also show that UBE4B overexpression is often associated with amplification of its gene in human brain tumors. Our data indicate that amplification and overexpression of UBE4B represent previously undescribed molecular mechanisms of inactivation of p53 in brain tumors.

元の言語英語
ページ(範囲)347-355
ページ数9
ジャーナルNature medicine
17
発行部数3
DOI
出版物ステータス出版済み - 3 1 2011

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Ubiquitination
Tumors
Degradation
Brain Neoplasms
Brain
Neoplasms
Medulloblastoma
Amplification
Ependymoma
Gene encoding
Ubiquitin-Protein Ligases
Gene Amplification
p53 Genes
Ligases
Ubiquitin
Transcriptional Activation
Genes
Apoptosis
Growth

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

Wu, H., Pomeroy, S. L., Ferreira, M., Teider, N., Mariani, J., Nakayama, K. I., ... Leng, R. P. (2011). UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53. Nature medicine, 17(3), 347-355. https://doi.org/10.1038/nm.2283

UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53. / Wu, Hong; Pomeroy, Scott L.; Ferreira, Manuel; Teider, Natalia; Mariani, Juliana; Nakayama, Keiichi I.; Hatakeyama, Shigetsugu; Tron, Victor A.; Saltibus, Linda F.; Spyracopoulos, Leo; Leng, Roger P.

:: Nature medicine, 巻 17, 番号 3, 01.03.2011, p. 347-355.

研究成果: ジャーナルへの寄稿記事

Wu, H, Pomeroy, SL, Ferreira, M, Teider, N, Mariani, J, Nakayama, KI, Hatakeyama, S, Tron, VA, Saltibus, LF, Spyracopoulos, L & Leng, RP 2011, 'UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53', Nature medicine, 巻. 17, 番号 3, pp. 347-355. https://doi.org/10.1038/nm.2283
Wu H, Pomeroy SL, Ferreira M, Teider N, Mariani J, Nakayama KI その他. UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53. Nature medicine. 2011 3 1;17(3):347-355. https://doi.org/10.1038/nm.2283
Wu, Hong ; Pomeroy, Scott L. ; Ferreira, Manuel ; Teider, Natalia ; Mariani, Juliana ; Nakayama, Keiichi I. ; Hatakeyama, Shigetsugu ; Tron, Victor A. ; Saltibus, Linda F. ; Spyracopoulos, Leo ; Leng, Roger P. / UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53. :: Nature medicine. 2011 ; 巻 17, 番号 3. pp. 347-355.
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