AKT1 modulates the nuclear distribution of the Heterochromatin Protein 1α and the pluripotency

ROBERTI SL, FRANCIA MG, ROVNER FA, DÍAZ MC, OSES C, COZZA LH, ARANOVICH M, ORSINGHER V, LEVI V, GUBERMAN AS.

Congreso; LASDB 2024; 2024

AKT is a serine-threonine kinase that regulates diverse processes in various cell types. In mouse embryonic stem cells (mESCs), it plays a key role in maintaining pluripotency. AKT activity is modulated by different mechanisms, including its SUMOylation. We have previously found that AKT1 induces the expression of the pluripotency transcription factor (TF) Nanog in a SUMOylation dependent manner, and that this post-translational modification promote AKT1 nuclear localization. Interestingly, these features are increased in the hyperactive E17K AKT1 mutant, present in many cancer cells. We hypothesize that both SUMOylation and the E17K mutation affect nuclear parameters that affect gene expression in mESCs. Here, we studied the effect of AKT1 variants with different SUMOylability and including or not the E17K mutation on the distribution of the Heterochromatin Protein 1α (HP1α) and the pluripotency TFs SOX2 and OCT4 by quantitative confocal microscopy analysis. We found that each AKT1 variant promoted different changes in the nuclear distribution of HP1α, suggesting a chromatin reorganization. We also found changes in the organization of OCT4 and SOX2. Therefore, we analysed the protein levels of these TFs by immunofluorescence. Remarkably, we found no effect of AKT1 variants on SOX2 and OCT4 expression, contrary to AKT1 induction of Nanog gene expression. These findings suggest that AKT1 modulates the chromatin landscape in a SUMOylation dependent manner. Additionally, the E17K mutant promoted the most prominent changes. Remarkably, the effect of this nuclear reorganization seems to have a specific effect, having an impact on Nanog gene expression, rather than affecting all the pluripotency TFs.