The abstract is read at the publisher; the summary is JClub's.
Fumarate hydratase (FH) deficiency in clear cell renal cell carcinoma (ccRCC) drives fumarate accumulation that remodels the ubiquitinated proteome and increases ferroptosis resistance.
- Why it matters: ccRCC shows intrinsic ferroptosis sensitivity, but the mechanism by which tumors escape this vulnerability is unclear.
- What they did: FH deficiency elevates fumarate, which induces C706 succination of UBA1, impairs UBA1–UBE2G2 interaction, and globally reduces ubiquitination, increasing ATF4 and SLC7A11.
- The result: A designed cell-penetrating peptide that attenuates fumarate-induced UBA1 succination suppresses the ATF4–SLC7A11 axis and enhances ferroptosis sensitivity, suggesting therapeutic targeting.
The findingWhy it mattersWhat they didThe result
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