(The) effect of AMPK-Ctbp2 interaction on embryonic stem cell pluripotency

[摘要] Stem cells undergo dynamic change of metabolic phenotype during differentiation and this feature reveals that metabolic status have pivotal role in maintain stemness. AMPK (AMP-activated protein kinase) is energy sensing kinase which is activated in energy deprivation by recognizing cellular energy status. However, that function in stem cell is not well understood. Ctbp (C-terminal binding protein) is co-repressor which regulates transcriptional activity of various gene. Previous reports reveal that Ctbp2 has a crucial role in stem cell differentiation. Furthermore, AMPK impedes Ctbp1 activity by phosphorylation. In this study, we hypothesize that in stem cells, AMPK regulates exit from pluripotency through Ctbp2 phosphorylation by energy dependent manner. First, we observed that Ctbp1 S158 residue which is phosphorylated by AMPK is conserved in Ctbp2 S164 and that residue is also phosphorylated by AMPK. Ctbp2 which is phosphorylated at S164 fails to dimerize and dissociates with NuRD complex. As a result of this, stem cell exhibits delayed differentiation. Consequently, AMPK recognizes cellular energy state and modulates differentiation through Ctbp2. It implies that stem cells have mechanism that impede differentiation in unstable state.

[发布机构] University:서울대학교 대학원

[效力级别] Energy

[关键词] Stem cell;Energy;AMPK;Ctbp;575