Nonstop mutations cause loss of renal tumor suppressor proteins <i>VHL</i> and <i>BAP1</i> and affect multiple stages of protein translation.

ABSTRACT: Nonstop extension or stop-loss mutations lead to the extension of a protein at its carboxyl terminus. Recently, nonstop mutations in the tumor suppressor SMAD Family Member 4 (SMAD4) have been discovered to lead to proteasomal SMAD4 degradation. However, this mutation type has not been studied in other cancer genes. Here, we explore somatic nonstop mutations in the tumor suppressor genes BRCA1 Associated Protein 1 (BAP1) and Von Hippel-Lindau (VHL) enriched in renal cell carcinoma. For BAP1, nonstop mutations generate an extremely long extension. Instead of proteasomal degradation, the extension decreases translation and depletes BAP1 messenger RNA from heavy polysomes. For VHL, the short extension leads to proteasomal degradat

SUBMITTER: Pal J 

PROVIDER: S-EPMC11817944 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature