Related Experiment Video
Updated: May 16, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
Published on: December 30, 2025
Diamond-Blackfan anemia gene product RPS19 counteracts SET to maintain p53 transcriptional activity and tumor
Hiroki Fujiyama1, Takuya Takafuji1, Ryoma Kokubo1
1Department of Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
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.
Insights
Diamond-Blackfan anemia (DBA) gene RPS19 acts as a tumor suppressor by counteracting the SET oncoprotein. RPS19 mutations found in cancer disrupt this function, highlighting its role in preventing cell transformation.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Diamond-Blackfan anemia (DBA) is a ribosomopathy linked to cancer predisposition.
- The RPS19 gene is frequently mutated in DBA, but its role in tumor suppression is not well understood.
Purpose of the Study:
- To investigate the tumor suppressor function of RPS19.
- To elucidate the mechanism by which RPS19 prevents cell transformation.
Main Methods:
- Cell transformation assays using human cells.
- Analysis of RPS19 interaction with SET oncoprotein.
- Investigation of RPS19's effect on p53 transcriptional activity and histone acetylation.
Main Results:
- RPS19 prevents human cell transformation by counteracting SET oncoprotein-mediated suppression of p53.
- Silencing RPS19 promotes transformation, while its overexpression inhibits cancer cell growth.
- Mutations in RPS19 found in cancer abrogate its binding to SET and tumor suppressor activity.
- RPS19 binds to p53 promoters and prevents SET-mediated histone hypoacetylation.
Conclusions:
- RPS19 possesses a critical tumor suppressor function.
- RPS19 counteracts SET oncoprotein to maintain p53 activity and prevent cell transformation.
- Dysregulation of RPS19 contributes to cancer development.
Related Concept Videos
Abnormal Proliferation
Negative Regulator Molecules
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
DNA Damage can Stall the Cell Cycle

