Growing and dividing: how O-GlcNAcylation leads the way.

Autor: Saunders H; Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas, USA., Dias WB; Federal University of Rio De Janeiro, Rio De Janeiro, Brazil; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, USA., Slawson C; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, USA. Electronic address: cslawson@kumc.edu.
Jazyk: angličtina
Zdroj: The Journal of biological chemistry [J Biol Chem] 2023 Nov; Vol. 299 (11), pp. 105330. Date of Electronic Publication: 2023 Oct 12.
DOI: 10.1016/j.jbc.2023.105330
Abstrakt: Cell cycle errors can lead to mutations, chromosomal instability, or death; thus, the precise control of cell cycle progression is essential for viability. The nutrient-sensing posttranslational modification, O-GlcNAc, regulates the cell cycle allowing one central control point directing progression of the cell cycle. O-GlcNAc is a single N-acetylglucosamine sugar modification to intracellular proteins that is dynamically added and removed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. These enzymes act as a rheostat to fine-tune protein function in response to a plethora of stimuli from nutrients to hormones. O-GlcNAc modulates mitogenic growth signaling, senses nutrient flux through the hexosamine biosynthetic pathway, and coordinates with other nutrient-sensing enzymes to progress cells through Gap phase 1 (G 1 ). At the G 1 /S transition, O-GlcNAc modulates checkpoint control, while in S Phase, O-GlcNAcylation coordinates the replication fork. DNA replication errors activate O-GlcNAcylation to control the function of the tumor-suppressor p53 at Gap Phase 2 (G 2 ). Finally, in mitosis (M phase), O-GlcNAc controls M phase progression and the organization of the mitotic spindle and midbody. Critical for M phase control is the interplay between OGT and OGA with mitotic kinases. Importantly, disruptions in OGT and OGA activity induce M phase defects and aneuploidy. These data point to an essential role for the O-GlcNAc rheostat in regulating cell division. In this review, we highlight O-GlcNAc nutrient sensing regulating G 1 , O-GlcNAc control of DNA replication and repair, and finally, O-GlcNAc organization of mitotic progression and spindle dynamics.
Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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