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- Title
O-Sialoglycoprotein Endopeptidase Deficiency Impairs Proteostasis and Induces Autophagy in Human Embryonic Stem Cells.
- Authors
Teng, Hua; Chen, Siyi; Liu, Fang; Teng, Yanling; Li, Yunlong; Liang, Desheng; Wu, Lingqian; Li, Zhuo
- Abstract
The OSGEP gene encodes O-sialoglycoprotein endopeptidase, a catalytic unit of the highly conserved KEOPS complex (Kinase, Endopeptidase, and Other Proteins of small Size) that regulates the second biosynthetic step in the formation of N-6-threonylcarbamoyladenosine (t6A). Mutations in KEOPS cause Galloway–Mowat syndrome (GAMOS), whose cellular function in mammals and underlying molecular mechanisms are not well understood. In this study, we utilized lentivirus-mediated OSGEP knockdown to generate OSGEP-deficient human embryonic stem cells (hESCs). OSGEP-knockdown hESCs exhibited reduced stemness factor expression and G2/M phase arrest, indicating a potential role of OSGEP in the regulation of hESC fate. Additionally, OSGEP silencing led to enhanced protein synthesis and increased aggregation of proteins, which further induced inappropriate autophagy, as evidenced by the altered expression of P62 and the conversion of LC3-I to LC3-II. The above findings shed light on the potential involvement of OSGEP in regulating pluripotency and differentiation in hESCs while simultaneously highlighting its crucial role in maintaining proteostasis and autophagy, which may have implications for human disease.
- Subjects
HUMAN embryonic stem cells; EMBRYONIC stem cells; AUTOPHAGY; CELL physiology; PROTEIN synthesis
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 14, p7889
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25147889