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O‐GlcNAc modification of proteins in mouse embryonic neural stem cells
Author(s) -
Yanagisawa Makoto,
Yu Robert K
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.693.7
Subject(s) - embryonic stem cell , biology , microbiology and biotechnology , neural stem cell , transcription factor , serine , stem cell , neuroepithelial cell , cellular differentiation , signal transduction , cell growth , programmed cell death , threonine , protein kinase b , cell fate determination , biochemistry , apoptosis , phosphorylation , gene
In neural stem cells (NSCs), glycoconjugates and carbohydrate antigens are known to serve as excellent biomarkers for cellular differentiation and to play functional roles in determining cell fate. O‐Linked β‐N‐acetylglucosamine (O‐GlcNAc) modifying nuclear and cytoplasmic proteins on the serine/threonine residues is also expected to play the regulatory roles. It is not known, however, if O‐GlcNAc modification is expressed in NSCs and what the function of this expression is. In this study, we evaluated the patterns and possible functions O‐GlcNAcylation in mouse embryonic neuroepithelial cells (NECs) which are rich in NSCs. We found the expression of O‐GlcNAc transferase, O‐GlcNAcase, and a number of O‐GlcNAcylated proteins in NECs. Treatment of NECs with O‐GlcNAcase inhibitors induced robust O‐GlcNAc accumulation in NECs and reduction of the cell number. In O‐GlcNAcase inhibitor‐treated NECs, the Ras‐MAPK pathway and the PI3K‐Akt pathway, important for proliferation and survival, respectively, were intact, but caspase‐3, an executioner of cell death, was activated. These results suggest that O‐GlcNAc is involved in cell death signaling in NECs. Furthermore, we identified an O‐GlcNAc‐modified protein, Sp1 transcription factor. This work was supported by USPHS grants NS11853, AG027199 and a grant from the Childrens' Medical Research Foundation, Chicago, IL.