相扑蛋白
细胞生物学
同源盒蛋白纳米
生物
亚细胞定位
染色质
蛋白激酶B
磷酸化
转录因子
胚胎干细胞
细胞质
诱导多能干细胞
生物化学
泛素
DNA
基因
作者
Marcos Francia,Camila Oses,Sabrina Lorena Roberti,Mora Reneé García,Lucas Helio Cozza,María Candelaria Diaz,Valeria Levi,Alejandra Guberman
标识
DOI:10.1016/j.jsb.2023.107961
摘要
AKT/PKB is a kinase involved in the regulation of a plethora of cell processes. Particularly, in embryonic stem cells (ESCs), AKT is crucial for the maintenance of pluripotency. Although the activation of this kinase relies on its recruitment to the cellular membrane and subsequent phosphorylation, multiple other post-translational modifications (PTMs), including SUMOylation, fine-tune its activity and target specificity. Since this PTM can also modify the localization and availability of different proteins, in this work we explored if SUMOylation impacts on the subcellular compartmentalization and distribution of AKT1 in ESCs. We found that this PTM does not affect AKT1 membrane recruitment, but it modifies the AKT1 nucleus/cytoplasm distribution, increasing its nuclear presence. Additionally, within this compartment, we found that AKT1 SUMOylation also impacts on the chromatin-binding dynamics of NANOG, a central pluripotency transcription factor. Remarkably, the oncogenic E17K AKT1 mutant produces major changes in all these parameters increasing the binding of NANOG to its targets, also in a SUMOylation dependent manner. These findings demonstrate that SUMOylation modulates AKT1 subcellular distribution, thus adding an extra layer of regulation of its function, possibly by affecting the specificity and interaction with its downstream targets.
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