Heterozygous loss-of-function alleles associate the conserved 3'-5' exoribonuclease EXOSC10 with hypersensitivity to the anticancer drug 5-fluorouracil - PubMed
3 days ago
- #5-fluorouracil
- #cancer
- #EXOSC10
- EXOSC10, a 3'-5' exoribonuclease, degrades aberrant RNAs and is essential for cell growth, fertility, hematopoiesis, and brain development.
- EXOSC10 is a cancer biomarker; its activity is inhibited by the anticancer drug 5-fluorouracil (5-FU), and depletion sensitizes cells to 5-FU.
- Mass spectrometry identified post-translational modifications (phosphorylation, acetylation, ubiquitination) and protein interactions of EXOSC10.
- The EXOSC10S402T allele, found in colon cancer, is stable and nuclear but nonfunctional, causing embryonic lethality in homozygous mice.
- Heterozygous loss-of-function alleles in EXOSC10 are linked to increased 5-FU sensitivity in tumors and hypertoxicity in carriers.