The abstract is read at the publisher; the summary is JClub's.
FBXO45-mediated K63 ubiquitination of HYOU1 sustains persistent UPR signaling and promotes acquired chemoresistance in gastric cancer models.
- Why it matters: UPR activation is linked to tumor progression and drug resistance, but the post-translational mechanisms shaping UPR dynamics in acquired resistance are unclear.
- What they did: In gastric cancer, immunoprecipitation-mass spectrometry mapped interactions among HYOU1, FBXO45, and PPM1B; FBXO45 then ubiquitinates HYOU1 with K63 linkages to recruit HSPs under endoplasmic reticulum stress.
- The result: HYOU1 ubiquitination increases PPM1B accessibility, inhibiting dephosphorylation of PERK and IRE1α to sustain UPR activation, and disrupting the FBXO45–HYOU1–PPM1B axis restores drug sensitivity in chemoresistant models.
The findingWhy it mattersWhat they didThe result
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