USP7 modulates K63 polyubiquitination of mTOR, which is essential for human pluripotent stem cell function
Release date:
2024-07-16
Description:
Here, we reveal that USP7, a deubiquitinase, directly modulates mTOR activity, the key driver of protein synthesis, in human embryonic stem cells (hESCs) and is essential for hESC function. USP7 directly modulates mTOR activity through K63-linked polyubiquitination. USP7-/- hESCs exhibit elevated ribosome assembly and protein synthesis, which impairs their fate specification into the three embryonic germ layers. Furthermore, we reveal an immediate downregulation of K63-linked polyubiquitination and protein synthesis prior to transcriptional changes at early differentiation onset in hESCs. Finally, we demonstrate the essential role of USP7 in regulating the translational switch during pluripotency exit. In summary, we identify USP7 and its noncanonical K63-linked polyubiquitination as a novel cell-intrinsic translational control mechanism essential for stem cell function.
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Organization: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Submission date: 2022-07-16
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