Journal article
Identification of novel plant cysteine oxidase inhibitors from a yeast chemical genetic screen
- Abstract:
-
Hypoxic responses in plants involve Plant Cysteine Oxidases (PCOs). They catalyze the N-terminal cysteine oxidation of Ethylene Response Factors VII (ERF-VII) in an oxygen-dependent manner, leading to their degradation via the cysteine N-degron pathway (Cys-NDP) in normoxia. In hypoxia, PCO activity drops, leading to the stabilization of ERF-VIIs and subsequent hypoxic gene upregulation. Thus far, no chemicals have been described to specifically inhibit PCO enzymes. In this work, we devised an in vivo pipeline to discover Cys-NDP effector molecules. Budding yeast expressing AtPCO4 and plant-based ERF-VII reporters was deployed to screen a library of natural-like chemical scaffolds and was further combined with an Arabidopsis Cys-NDP reporter line. This strategy allowed us to identify three PCO inhibitors, two of which were shown to affect PCO activity in vitro. Application of these molecules to Arabidopsis seedlings led to an increase in ERF-VII stability, induction of anaerobic gene expression, and improvement of tolerance to anoxia. By combining a high-throughput heterologous platform and the plant model Arabidopsis, our synthetic pipeline provides a versatile system to study how the Cys-NDP is modulated. Its first application here led to the discovery of at least two hypoxia-mimicking molecules with the potential to impact plant tolerance to low oxygen stress.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 2.4MB, Terms of use)
-
- Publisher copy:
- 10.1016/j.jbc.2023.105366
Authors
- Publisher:
- Elsevier
- Journal:
- Journal of Biological Chemistry More from this journal
- Volume:
- 299
- Issue:
- 12
- Article number:
- 105366
- Publication date:
- 2023-10-19
- Acceptance date:
- 2023-10-11
- DOI:
- EISSN:
-
1083-351X
- ISSN:
-
0021-9258
- Pmid:
-
37863264
- Language:
-
English
- Keywords:
- Pubs id:
-
1552599
- Local pid:
-
pubs:1552599
- Deposit date:
-
2024-01-03
- ARK identifier:
Terms of use
- Copyright holder:
- Lavilla-Puerta et al.
- Copyright date:
- 2023
- Rights statement:
- © 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
If you are the owner of this record, you can report an update to it here: Report update to this record