| RRC ID |
89476
|
| Author |
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.
|
| Title |
Diamond-Blackfan anemia gene product RPS19 counteracts SET to maintain p53 transcriptional activity and tumor suppressor function.
|
| Journal |
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.
|
| Volume |
45(5)
|
| Pages |
117333
|
| Published |
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
|
| Resource |
| DNA material |
Genome Network Project (GNP) Human cDNA IRAK069P02 (HGX027962) |
