GRWD1 negatively regulates p53 via the RPL11–MDM2 pathway and promotes tumorigenesis

Kota Kayama, Shinya Watanabe, Takuya Takafuji, Takahiro Tsuji, Kensuke Hironaka, Masaki Matsumoto, Keiichi Nakayama, Masato Enari, Takashi Kohno, Kouya Shiraishi, Tohru Kiyono, Kazumasa Yoshida, Nozomi Sugimoto, Masatoshi Fujita

研究成果: ジャーナルへの寄稿記事

9 引用 (Scopus)

抄録

The ribosomal protein L11 (RPL11) binds and inhibits the MDM2 ubiquitin ligase, thereby promoting p53 stability. Thus, RPL11 acts as a tumor suppressor. Here, we show that GRWD1 (glutamate-rich WD40 repeat containing 1) physically and functionally interacts with RPL11. GRWD1 is localized to nucleoli and is released into the nucleoplasm upon nucleolar stress. Silencing of GRWD1 increases p53 induction by nucleolar stress, whereas overexpression of GRWD1 reduces p53 induction. Furthermore, GRWD1 overexpression competitively inhibits the RPL11–MDM2 interaction and alleviates RPL11-mediated suppression of MDM2 ubiquitin ligase activity toward p53. These effects are mediated by the N-terminal region of GRWD1, including the acidic domain. Finally, we show that GRWD1 overexpression in combination with HPV16 E7 and activated KRAS confers anchorage-independent growth and tumorigenic capacity on normal human fibroblasts. Consistent with this, GRWD1 overexpression is associated with poor prognosis in cancer patients. Taken together, our results suggest that GRWD1 is a novel negative regulator of p53 and a potential oncogene.

元の言語英語
ページ(範囲)123-137
ページ数15
ジャーナルEMBO Reports
18
発行部数1
DOI
出版物ステータス出版済み - 1 1 2017

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Glutamic Acid
Carcinogenesis
Ligases
Ubiquitin
WD40 Repeats
Fibroblasts
Oncogenes
Tumors
Neoplasms
ribosomal protein L11
Growth

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

これを引用

GRWD1 negatively regulates p53 via the RPL11–MDM2 pathway and promotes tumorigenesis. / Kayama, Kota; Watanabe, Shinya; Takafuji, Takuya; Tsuji, Takahiro; Hironaka, Kensuke; Matsumoto, Masaki; Nakayama, Keiichi; Enari, Masato; Kohno, Takashi; Shiraishi, Kouya; Kiyono, Tohru; Yoshida, Kazumasa; Sugimoto, Nozomi; Fujita, Masatoshi.

:: EMBO Reports, 巻 18, 番号 1, 01.01.2017, p. 123-137.

研究成果: ジャーナルへの寄稿記事

Kayama, K, Watanabe, S, Takafuji, T, Tsuji, T, Hironaka, K, Matsumoto, M, Nakayama, K, Enari, M, Kohno, T, Shiraishi, K, Kiyono, T, Yoshida, K, Sugimoto, N & Fujita, M 2017, 'GRWD1 negatively regulates p53 via the RPL11–MDM2 pathway and promotes tumorigenesis', EMBO Reports, 巻. 18, 番号 1, pp. 123-137. https://doi.org/10.15252/embr.201642444
Kayama, Kota ; Watanabe, Shinya ; Takafuji, Takuya ; Tsuji, Takahiro ; Hironaka, Kensuke ; Matsumoto, Masaki ; Nakayama, Keiichi ; Enari, Masato ; Kohno, Takashi ; Shiraishi, Kouya ; Kiyono, Tohru ; Yoshida, Kazumasa ; Sugimoto, Nozomi ; Fujita, Masatoshi. / GRWD1 negatively regulates p53 via the RPL11–MDM2 pathway and promotes tumorigenesis. :: EMBO Reports. 2017 ; 巻 18, 番号 1. pp. 123-137.
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AU - Hironaka, Kensuke

AU - Matsumoto, Masaki

AU - Nakayama, Keiichi

AU - Enari, Masato

AU - Kohno, Takashi

AU - Shiraishi, Kouya

AU - Kiyono, Tohru

AU - Yoshida, Kazumasa

AU - Sugimoto, Nozomi

AU - Fujita, Masatoshi

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