{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:50:15Z","timestamp":1778575815580,"version":"3.51.4"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Naito Foundation, Fukuoka Foundation for Sound Health Cancer Research Fund, and the Shin-Nihon Foundation of Advanced Medical Research"},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18K07201"],"award-info":[{"award-number":["JP18K07201"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a novel oncogene\/oncoprotein that downregulates the p53 tumour suppressor protein through several mechanisms. One important mechanism involves binding of GRWD1 to RPL11, which competitively inhibits the RPL11\u2013MDM2 interaction and releases RPL11-mediated suppression of MDM2 ubiquitin ligase activity towards p53. Here, we mined the TCGA (The Cancer Genome Atlas) database to gain in-depth insight into the clinical relevance of GRWD1. We found that high expression of GRWD1 is associated with a poor prognosis for lower grade glioma (LGG) of the brain, skin cutaneous melanoma (SKCM), and kidney renal clear cell carcinoma (KIRC) carrying wild-type p53. Further investigations revealed that copy number alterations in the GRWD1 gene are one determinant of GRWD1 expression level. By contrast, even in patients with a diploid GRWD1 gene, high GRWD1 expression was associated with a poor prognosis for LGG, SKCM, and KIRC carrying wild-type p53. Additional studies suggest that some transcriptional factors may be involved in regulation of GRWD1 in cancers with a diploid GRWD1 gene. Taken together, the data presented herein suggest that high expression of GRWD1 may contribute to malignant behaviour, and predict a clinically unfavourable prognosis for LGG, SKCM, and KIRC carrying wild-type p53.<\/jats:p>","DOI":"10.1093\/jb\/mvaf004","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T15:28:41Z","timestamp":1736954921000},"page":"351-361","source":"Crossref","is-referenced-by-count":2,"title":["High <i>GRWD1<\/i> expression may predict clinically aggressive lower grade glioma, skin cutaneous melanoma, and kidney renal clear cell carcinoma carrying wild-type p53: a systematic study based on TCGA data analysis"],"prefix":"10.1093","volume":"177","author":[{"given":"Kota","family":"Kayama","sequence":"first","affiliation":[{"name":"Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Ooga","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kouji","family":"Hasetsu","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoma","family":"Kokubo","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nozomi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"2025042808421205800_ref1","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.cell.2008.05.020","article-title":"p53 posttranslational modifications","volume":"133","author":"Kruse","year":"2009","journal-title":"Cell"},{"key":"2025042808421205800_ref2","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nrm2395","article-title":"Transcriptional control of human p53-regulated genes","volume":"9","author":"Riley","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2025042808421205800_ref3","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.ygeno.2005.02.010","article-title":"The WD-repeat protein GRWD1: potential roles in myeloid differentiation and ribosome biogenesis","volume":"85","author":"Gratenstein","year":"2005","journal-title":"Genomics"},{"key":"2025042808421205800_ref4","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1128\/MCB.21.4.1260-1271.2001","article-title":"Rrb1p, a yeast nuclear WD-repeat protein involved in the regulation of ribosome biosynthesis","volume":"21","author":"Iouk","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"2025042808421205800_ref5","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/S0960-9822(01)00584-X","article-title":"A yeast homolog of chromatin assembly factor 1 is involved in early ribosome assembly","volume":"11","author":"Schaper","year":"2001","journal-title":"Curr. Biol."},{"key":"2025042808421205800_ref6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.15252\/embr.201642444","article-title":"GRWD 1 negatively regulates p53 via the RPL 11\u2013 MDM 2 pathway and promotes tumorigenesis","volume":"18","author":"Kayama","year":"2017","journal-title":"EMBO Rep."},{"key":"2025042808421205800_ref7","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.213009","article-title":"GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system","volume":"131","author":"Watanabe","year":"2018","journal-title":"J. Cell Sci."},{"key":"2025042808421205800_ref8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/jb\/mvz075","article-title":"GRWD1 directly interacts with p53 and negatively regulates p53 transcriptional activity","volume":"220","author":"Fujiyama","year":"2020","journal-title":"J. Biochem."},{"key":"2025042808421205800_ref9","article-title":"SPIN1 promotes tumorigenesis by blocking the uL18 (universal large ribosomal subunit protein 18)-MDM2-p53 pathway in human cancer","volume":"21","author":"Fang","year":"2018","journal-title":"elife"},{"key":"2025042808421205800_ref10","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/nm.2392","article-title":"Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11","volume":"17","author":"Sasaki","year":"2011","journal-title":"Nat. Med."},{"key":"2025042808421205800_ref11","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/8201377","article-title":"Comprehensive analysis of glutamate-rich WD repeat-containing protein 1 and its potential clinical significance for Pancancer","volume":"2021","author":"Wu","year":"2021","journal-title":"Biomed. Res. 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Rev. Clin. Oncol."},{"key":"2025042808421205800_ref19","doi-asserted-by":"crossref","first-page":"102668","DOI":"10.1016\/j.ctrv.2023.102668","article-title":"MDM2-p53 in liposarcoma: the need for targeted therapies with novel mechanisms of action","volume":"122","author":"Somaiah","year":"2024","journal-title":"Cancer Treat. Rev."}],"container-title":["The Journal of Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jb\/advance-article-pdf\/doi\/10.1093\/jb\/mvaf004\/61442154\/mvaf004.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jb\/article-pdf\/177\/5\/351\/61442154\/mvaf004.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jb\/article-pdf\/177\/5\/351\/61442154\/mvaf004.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T12:42:23Z","timestamp":1745844143000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jb\/article\/177\/5\/351\/7954444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":19,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,1,15]]},"published-print":{"date-parts":[[2025,4,29]]}},"URL":"https:\/\/doi.org\/10.1093\/jb\/mvaf004","relation":{},"ISSN":["0021-924X","1756-2651"],"issn-type":[{"value":"0021-924X","type":"print"},{"value":"1756-2651","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5]]},"published":{"date-parts":[[2025,1,15]]}}}