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Inducible protein degradation systems are an important but untapped resource for the study of protein function in plant cells. Unlike mutagenesis or transcriptional control, regulated degradation of proteins of interest allows the study of the biological mechanisms of highly dynamic cellular processes involving essential proteins. While systems for targeted protein degradation are available for research and therapeutics in animals, there are currently limited options in plant biology. Targeted protein degradation systems rely on target ubiquitination by E3 ubiquitin ligases. Systems that are available or being developed in plants can be distinguished primarily by the type of E3 ubiquitin ligase involved, including those that utilize Cullin-RING ligases, bacterial novel E3 ligases, and N-end rule pathway E3 ligases, or they can be controlled by proteolysis targeting chimeras. Target protein ubiquitination leads to degradation by the proteasome or targeting to the vacuole, with both pathways being ubiquitous and important for the endogenous control of protein abundance in plants. Targeted proteolysis approaches for plants will likely be an important tool for basic research and to yield novel traits for crop biotechnology.
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Regulation of O-Linked N-Acetyl Glucosamine Transferase (OGT) through E6 Stimulation of the Ubiquitin Ligase Activity of E6AP
Glycosyltransferase OGT catalyzes the conjugation of O-linked β-D-N-acetylglucosamine (O-GlcNAc) to Ser and Thr residues of the cellular proteins and regulates many key processes in the cell. Here, we report the identification of OGT as a ubiquitination target of HECT-type E3 ubiquitin (UB) ligase E6AP, whose overexpression in HEK293 cells would induce the degradation of OGT. We also found that the expression of E6AP in HeLa cells with the endogenous expression of the E6 protein of the human papillomavirus (HPV) would accelerate OGT degradation by the proteasome and suppress O-GlcNAc modification of OGT substrates in the cell. Overall, our study establishes a new mechanism of OGT regulation by the ubiquitin–proteasome system (UPS) that mediates the crosstalk between protein ubiquitination and O-GlcNAcylation pathways underlying diverse cellular processes.
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- PAR ID:
- 10302297
- Date Published:
- Journal Name:
- International Journal of Molecular Sciences
- Volume:
- 22
- Issue:
- 19
- ISSN:
- 1422-0067
- Page Range / eLocation ID:
- 10286
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.3390/ijms221910286
