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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]

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