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.

Cell Reports
|May 14, 2026
PubMed

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.

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