2026-05-14 九州大学
図1：RPS19による細胞がん化抑制メカニズム
RPS19遺伝子変異によりそのタンパク質機能が損なわれると、SETの機能が過剰となり、細胞増殖のブレーキであるp53機能が低下して細胞がん化が促進される。
＜関連情報＞
- https://www.kyushu-u.ac.jp/ja/researches/view/1474
- https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00411-0
ダイアモンド・ブラックファン貧血遺伝子産物RPS19はSETに対抗し、p53転写活性と腫瘍抑制機能を維持する Diamond-Blackfan anemia gene product RPS19 counteracts SET to maintain p53 transcriptional activity and tumor suppressor function
Hiroki Fujiyama ∙ Takuya Takafuji ∙ Ryoma Kokubo ∙ … ∙ Hidetaka Kosako ∙ Nozomi Sugimoto ∙ Masatoshi Fujita
Cell Reports Published:May 13, 2026
DOI:https://doi.org/10.1016/j.celrep.2026.117333
Highlights
- Diamond-Blackfan anemia is a ribosomopathy associated with cancer predisposition
- RPS19 is the most commonly mutated gene in Diamond-Blackfan anemia
- RPS19 prevents oncogenesis by counteracting SET-mediated attenuation of p53 activity
- RPS19 binds to p53-responsive promoters and negates SET-mediated histone hypoacetylation
Summary
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.
