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RRC ID 89476
著者 Fujiyama H, Takafuji T, Kokubo R, Yanagi N, Mori Y, Tsutsui N, Okuyama Y, Nakahara Y, Kiyono T, Katsuki Y, Yoshida K, Kosako H, Sugimoto N, Fujita M.
タイトル Diamond-Blackfan anemia gene product RPS19 counteracts SET to maintain p53 transcriptional activity and tumor suppressor function.
ジャーナル Cell Rep
Abstract Diamond-Blackfan anemia (DBA), a congenital ribosomopathy, is associated with a predisposition to cancer. The most commonly mutated gene in DBA is RPS19; however, it remains unclear whether RPS19 actually functions as a tumor suppressor and, if so, by what mechanism. Here, we show that RPS19 prevents human cell transformation by counteracting SET oncoprotein-mediated attenuation of p53 transcriptional activity. Thus, silencing RPS19, in combination with expression of HPV16 E7 and activated KRAS G12V, transforms normal human cells; conversely, its overexpression inhibits cancer cell growth in a p53-dependent manner. RPS19 binds to SET and counteracts SET-mediated inhibition of p53 transcriptional activity. Importantly, we find that point mutations in RPS19, which are recurrently found in cancer cells, specifically abrogate its binding to SET and tumor suppressor function. Mechanistically, RPS19 binds to the p53-responsive promoters, where it counteracts SET-mediated histone hypoacetylation. Together, these findings reveal a crucial tumor suppressor function of RPS19.
巻・号 45(5)
ページ 117333
公開日 2026-5-26
DOI 10.1016/j.celrep.2026.117333
PII S2211-1247(26)00411-0
PMID 42134317
MeSH Anemia, Diamond-Blackfan* / genetics Anemia, Diamond-Blackfan* / metabolism Cell Line, Tumor Cell Transformation, Neoplastic / genetics Histones / metabolism Humans Promoter Regions, Genetic Protein Binding Ribosomal Proteins* / genetics Ribosomal Proteins* / metabolism Transcription, Genetic* Tumor Suppressor Protein p53* / genetics Tumor Suppressor Protein p53* / metabolism
リソース情報
遺伝子材料 Genome Network Project (GNP) Human cDNA IRAK069P02 (HGX027962)