ИСТИНА

Embryonic stem cells and induced pluripotent stem cells (iPSC) are not only interesting objects of fundamental research, but also extremely promising in various fields of applied medicine, regenerative medicine. Despite the great interest to pluripotent cells, the mechanisms of maintaining protein homeostasis in these cells by the ubiquitin-proteasome system have been studied rather poorly. The proteasome consists of a 20S core and regulatory 19S particles. Also the constitutive catalytic subunits β1, β2 and β5, can be replaced by alternative subunits - β1i, β2i and β5i and form immunoproteasome(IP). There is also an additional regulator - PA28α/β. The role of IP in the process of reprogramming of somatic cells into iPSC has been little studied. We induced reprogramming of mouse embryonic fibroblasts(MEFs) into iPSC and we observed the increase expression of β1i and β5i subunits. Furthermore, during the treatment with selective inhibitor of the β5i - PR-957 and inhibitor of β5 and β5i - MG-132, alkaline phosphatase staining showed a significant decrease in the formation of iPSC clones, which indicates the important functions of both proteasomes and IP in the reprogramming. Analysis of reprogramming of MEFs derived from β2i- and PA28α/β-deficient embryos also showed a strong decrease in the ability to give rise to iPSC clones, again, implying important functions of proteasomes, IP and PA28 in the process of reprogramming. This work was supported by RSF 16-04-10343