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The CTLH ubiquitin ligase substrates ZMYND19 and MKLN1 negatively regulate mTORC1 at the lysosomal membrane

Here they show that the E3 ubiquitin ligase CTLH supports mTORC1. Upon CTLH inactivation, ZMYND19 and MKLN19 accumulate, associate, and block mTORC1/RHEB association. CTLH and PI3K inhibition are synthetic lethal for EBV-associated gastric cancer.

Yin Wang
Yifei Liao
Benjamin E. Gewurz
ResearchOpen Access28 Nov 2025
Nature Communications

Volume: 16, P: 1-22

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The CTLH ubiquitin ligase substrates ZMYND19 and MKLN1 negatively regulate mTORC1 at the lysosomal membrane

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