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Ube2s regulates Sox2 stability and mouse ES cell maintenance.

ABSTRACT: Sox2 has a critical role in embryonic stem (ES) cell maintenance and differentiation. Interestingly, its activity is highly dosage-dependent. Although transcriptional regulation of Sox2 has been extensively studied, the mechanisms orchestrating its degradation remain unclear. In this study, we identified ubiquitin-conjugating enzyme E2S (Ube2s) as a novel effector for Sox2 protein degradation. Ube2s mediates K11-linked polyubiquitin chain formation at the Sox2-K123 residue, thus marking it for proteasome-mediated degradation. Besides its role in fine-tuning the precise level of Sox2, Ube2s reinforces the self-renewing and pluripotent state of ES cells. Importantly, it also represses Sox2-mediated ES cell differentiation toward the neural ectodermal lineage.

SUBMITTER: Wang J

PROVIDER: S-EPMC5072435 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Ube2s regulates Sox2 stability and mouse ES cell maintenance.

Wang J J Zhang Y Y Hou J J Qian X X Zhang H H Zhang Z Z Li M M Wang R R Liao K K Wang Y Y Li Z Z Zhong D D Wan P P Dong L L Liu F F Wang X X Wan Y Y Xiao W W Zhang W W WW

Cell death and differentiation 20150821 3

Sox2 has a critical role in embryonic stem (ES) cell maintenance and differentiation. Interestingly, its activity is highly dosage-dependent. Although transcriptional regulation of Sox2 has been extensively studied, the mechanisms orchestrating its degradation remain unclear. In this study, we identified ubiquitin-conjugating enzyme E2S (Ube2s) as a novel effector for Sox2 protein degradation. Ube2s mediates K11-linked polyubiquitin chain formation at the Sox2-K123 residue, thus marking it for p ...[more]

PMID: 26292759

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