Site-specific O-GlcNAcylation of Psme3 maintains mouse stem cell pluripotency by impairing P-body homeostasis
Federico Pecori,
Nanako Kondo,
Chika Ogura,
Taichi Miura,
Masahiko Kume,
Youhei Minamijima,
Kazuo Yamamoto,
Shoko Nishihara
Affiliations
Federico Pecori
Laboratory of Cell Biology, Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan
Nanako Kondo
Laboratory of Cell Biology, Department of Science and Engineering for Sustainable Innovation, Faculty of Science and Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan
Chika Ogura
Laboratory of Cell Biology, Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan
Taichi Miura
Laboratory of Cell Biology, Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan
Masahiko Kume
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
Youhei Minamijima
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
Kazuo Yamamoto
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan
Shoko Nishihara
Laboratory of Cell Biology, Department of Bioinformatics, Graduate School of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan; Laboratory of Cell Biology, Department of Science and Engineering for Sustainable Innovation, Faculty of Science and Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan; Glycan & Life System Integration Center (GaLSIC), Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan; Corresponding author
Summary: Mouse embryonic stem cell (ESC) pluripotency is tightly regulated by a complex network composed of extrinsic and intrinsic factors that allow proper organismal development. O-linked β-N-acetylglucosamine (O-GlcNAc) is the sole glycosylation mark found on cytoplasmic and nuclear proteins and plays a pivotal role in regulating fundamental cellular processes; however, its function in ESC pluripotency is still largely unexplored. Here, we identify O-GlcNAcylation of proteasome activator subunit 3 (Psme3) protein as a node of the ESC pluripotency network. Mechanistically, O-GlcNAc modification of serine 111 (S111) of Psme3 promotes degradation of Ddx6, which is essential for processing body (P-body) assembly, resulting in the maintenance of ESC pluripotent state. Conversely, loss of Psme3 S111 O-GlcNAcylation stabilizes Ddx6 and increases P-body levels, culminating in spontaneous exit of ESC from the pluripotent state. Our findings establish O-GlcNAcylation at S111 of Psme3 as a switch that regulates ESC pluripotency via control of P-body homeostasis.
