O-GlcNAcase is essential for embryonic development and maintenance of genomic stability
SCIE
SCOPUS
- Title
- O-GlcNAcase is essential for embryonic development and maintenance of genomic stability
- Authors
- Yang, YR; Minseok Song; Ho Lee; Yoon Jeon; Eun-Jeong Choi; Hyun-Jun Jang; Hyo Youl Moon; Ha-Young Byun; Eung-Kyun Kim; Dae Hyun Kim; Mi Nam Lee; Ara Koh; Jaewang Ghim; Jang Hyun Choi; Whaseon Lee-Kwon; Kim, KT; Sung Ho Ryu; Pann-Ghill Suh
- Date Issued
- 2012-06
- Publisher
- Blackwell Publishing Ltd
- Abstract
- Dysregulation of O-GlcNAc modification catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) contributes to the etiology of chronic diseases of aging, including cancer, cardiovascular disease, type 2 diabetes, and Alzheimers disease. Here we found that natural aging in wild-type mice was marked by a decrease in OGA and OGT protein levels and an increase in O-GlcNAcylation in various tissues. Genetic disruption of OGA resulted in constitutively elevated O-GlcNAcylation in embryos and led to neonatal lethality with developmental delay. Importantly, we observed that serum-stimulated cell cycle entry induced increased O-GlcNAcylation and decreased its level after release from G2/M arrest, indicating that O-GlcNAc cycling by OGT and OGA is required for precise cell cycle control. Constitutively, elevated O-GlcNAcylation by OGA disruption impaired cell proliferation and resulted in mitotic defects with downregulation of mitotic regulators. OGA loss led to mitotic defects including cytokinesis failure and binucleation, increased lagging chromosomes, and micronuclei formation. These findings suggest an important role for O-GlcNAc cycling by OGA in embryonic development and the regulation of the maintenance of genomic stability linked to the aging process.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/16661
- DOI
- 10.1111/j.1474-9726.2012.00801.x
- ISSN
- 1474-9718
- Article Type
- Article
- Citation
- AGING CELL, vol. 11, no. 3, page. 439 - 448, 2012-06
- Files in This Item:
-
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.