GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system

Shinya Watanabe, Hiroki Fujiyama, Takuya Takafuji, Kota Kayama, Masaki Matsumoto, Keiichi I. Nakayama, Kazumasa Yoshida, Nozomi Sugimoto, Masatoshi Fujita

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a Cdt1- binding protein that promotes mini-chromosome maintenance (MCM) loading through its histone chaperone activity. GRWD1 acts as a tumor-promoting factor by downregulating p53 (also known as TP53) via the RPL11-MDM2-p53 axis. Here, we identified GRWD1- interacting proteins using a proteomics approach and showed that GRWD1 interacts with various proteins involved in transcription, translation, DNA replication and repair, chromatin organization, and ubiquitin-mediated proteolysis. We focused on the ribosomal protein ribosomal protein L23 (RPL23), which positively regulates nucleolar stress responses through MDM2 binding and inhibition, thereby functioning as a tumor suppressor. Overexpression of GRWD1 decreased RPL23 protein levels and stability; this effect was restored upon treatment with the proteasome inhibitor MG132. EDD (also known as UBR5), an E3 ubiquitin ligase that interacts with GRWD1, also downregulated RPL23, and the decrease was further enhanced by co-expression of GRWD1. Conversely, siRNA-mediated GRWD1 knockdown upregulated RPL23. Co-expression of GRWD1 and EDD promoted RPL23 ubiquitylation. These data suggest that GRWD1 acts together with EDD to negatively regulate RPL23 via the ubiquitinproteasome system. GRWD1 expression reversed the RPL23- mediated inhibition of anchorage-independent growth in cancer cells. Our data suggest that GRWD1-induced RPL23 proteolysis plays a role in downregulation of p53 and tumorigenesis.

元の言語英語
ジャーナルJournal of Cell Science
131
発行部数15
DOI
出版物ステータス出版済み - 8 1 2018

Fingerprint

Ribosomal Proteins
Proteasome Endopeptidase Complex
Ubiquitin
Glutamic Acid
Down-Regulation
Proteolysis
WD40 Repeats
Histone Chaperones
Neoplasms
Proteasome Inhibitors
Ubiquitin-Protein Ligases
Protein Stability
Ubiquitination
DNA Replication
DNA Repair
Proteomics
Small Interfering RNA
Chromatin
Carrier Proteins
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Cell Biology

これを引用

GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system. / Watanabe, Shinya; Fujiyama, Hiroki; Takafuji, Takuya; Kayama, Kota; Matsumoto, Masaki; Nakayama, Keiichi I.; Yoshida, Kazumasa; Sugimoto, Nozomi; Fujita, Masatoshi.

:: Journal of Cell Science, 巻 131, 番号 15, 01.08.2018.

研究成果: ジャーナルへの寄稿記事

@article{bed6322bb5014cc5972c612d6a6a1a7d,
title = "GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system",
abstract = "Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a Cdt1- binding protein that promotes mini-chromosome maintenance (MCM) loading through its histone chaperone activity. GRWD1 acts as a tumor-promoting factor by downregulating p53 (also known as TP53) via the RPL11-MDM2-p53 axis. Here, we identified GRWD1- interacting proteins using a proteomics approach and showed that GRWD1 interacts with various proteins involved in transcription, translation, DNA replication and repair, chromatin organization, and ubiquitin-mediated proteolysis. We focused on the ribosomal protein ribosomal protein L23 (RPL23), which positively regulates nucleolar stress responses through MDM2 binding and inhibition, thereby functioning as a tumor suppressor. Overexpression of GRWD1 decreased RPL23 protein levels and stability; this effect was restored upon treatment with the proteasome inhibitor MG132. EDD (also known as UBR5), an E3 ubiquitin ligase that interacts with GRWD1, also downregulated RPL23, and the decrease was further enhanced by co-expression of GRWD1. Conversely, siRNA-mediated GRWD1 knockdown upregulated RPL23. Co-expression of GRWD1 and EDD promoted RPL23 ubiquitylation. These data suggest that GRWD1 acts together with EDD to negatively regulate RPL23 via the ubiquitinproteasome system. GRWD1 expression reversed the RPL23- mediated inhibition of anchorage-independent growth in cancer cells. Our data suggest that GRWD1-induced RPL23 proteolysis plays a role in downregulation of p53 and tumorigenesis.",
author = "Shinya Watanabe and Hiroki Fujiyama and Takuya Takafuji and Kota Kayama and Masaki Matsumoto and Nakayama, {Keiichi I.} and Kazumasa Yoshida and Nozomi Sugimoto and Masatoshi Fujita",
year = "2018",
month = "8",
day = "1",
doi = "10.1242/jcs.213009",
language = "English",
volume = "131",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "15",

}

TY - JOUR

T1 - GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system

AU - Watanabe, Shinya

AU - Fujiyama, Hiroki

AU - Takafuji, Takuya

AU - Kayama, Kota

AU - Matsumoto, Masaki

AU - Nakayama, Keiichi I.

AU - Yoshida, Kazumasa

AU - Sugimoto, Nozomi

AU - Fujita, Masatoshi

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a Cdt1- binding protein that promotes mini-chromosome maintenance (MCM) loading through its histone chaperone activity. GRWD1 acts as a tumor-promoting factor by downregulating p53 (also known as TP53) via the RPL11-MDM2-p53 axis. Here, we identified GRWD1- interacting proteins using a proteomics approach and showed that GRWD1 interacts with various proteins involved in transcription, translation, DNA replication and repair, chromatin organization, and ubiquitin-mediated proteolysis. We focused on the ribosomal protein ribosomal protein L23 (RPL23), which positively regulates nucleolar stress responses through MDM2 binding and inhibition, thereby functioning as a tumor suppressor. Overexpression of GRWD1 decreased RPL23 protein levels and stability; this effect was restored upon treatment with the proteasome inhibitor MG132. EDD (also known as UBR5), an E3 ubiquitin ligase that interacts with GRWD1, also downregulated RPL23, and the decrease was further enhanced by co-expression of GRWD1. Conversely, siRNA-mediated GRWD1 knockdown upregulated RPL23. Co-expression of GRWD1 and EDD promoted RPL23 ubiquitylation. These data suggest that GRWD1 acts together with EDD to negatively regulate RPL23 via the ubiquitinproteasome system. GRWD1 expression reversed the RPL23- mediated inhibition of anchorage-independent growth in cancer cells. Our data suggest that GRWD1-induced RPL23 proteolysis plays a role in downregulation of p53 and tumorigenesis.

AB - Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a Cdt1- binding protein that promotes mini-chromosome maintenance (MCM) loading through its histone chaperone activity. GRWD1 acts as a tumor-promoting factor by downregulating p53 (also known as TP53) via the RPL11-MDM2-p53 axis. Here, we identified GRWD1- interacting proteins using a proteomics approach and showed that GRWD1 interacts with various proteins involved in transcription, translation, DNA replication and repair, chromatin organization, and ubiquitin-mediated proteolysis. We focused on the ribosomal protein ribosomal protein L23 (RPL23), which positively regulates nucleolar stress responses through MDM2 binding and inhibition, thereby functioning as a tumor suppressor. Overexpression of GRWD1 decreased RPL23 protein levels and stability; this effect was restored upon treatment with the proteasome inhibitor MG132. EDD (also known as UBR5), an E3 ubiquitin ligase that interacts with GRWD1, also downregulated RPL23, and the decrease was further enhanced by co-expression of GRWD1. Conversely, siRNA-mediated GRWD1 knockdown upregulated RPL23. Co-expression of GRWD1 and EDD promoted RPL23 ubiquitylation. These data suggest that GRWD1 acts together with EDD to negatively regulate RPL23 via the ubiquitinproteasome system. GRWD1 expression reversed the RPL23- mediated inhibition of anchorage-independent growth in cancer cells. Our data suggest that GRWD1-induced RPL23 proteolysis plays a role in downregulation of p53 and tumorigenesis.

UR - http://www.scopus.com/inward/record.url?scp=85051595010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051595010&partnerID=8YFLogxK

U2 - 10.1242/jcs.213009

DO - 10.1242/jcs.213009

M3 - Article

VL - 131

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 15

ER -