The protein tyrosine phosphatase PPH‐7 is required for fertility and embryonic development in C. elegans at elevated temperatures

Post‐translational modifications are key in the regulation of activity, structure, localization, and stability of most proteins in eukaryotes. Phosphorylation is potentially the most studied post‐translational modification, also due to its reversibility and thereby the regulatory role this modificat...

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Bibliographic Details
Published in:FEBS open bio 2024-03, Vol.14 (3), p.390-409
Main Authors: Franziscus, Curdin A., Ritz, Danilo, Kappel, N. Constantin, Solinger, Jachen A., Schmidt, Alexander, Spang, Anne
Format: Article
Language:English
Subjects:
C. elegans
Cancer
Embryogenesis
Evolutionary conservation
Extracellular matrix
Fertility
Genomes
High temperature
Hypoxia
Kinases
Lethality
Localization
Mutation
Nematodes
Phosphatase
Phosphorylation
Post-translation
post‐translational modifications
Protein-tyrosine-phosphatase
Proteins
Proteomics
PTPN
Software
Temperature
Translation
Ubiquitin-protein ligase
Worms
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Summary:Post‐translational modifications are key in the regulation of activity, structure, localization, and stability of most proteins in eukaryotes. Phosphorylation is potentially the most studied post‐translational modification, also due to its reversibility and thereby the regulatory role this modification often plays. While most research attention was focused on kinases in the past, phosphatases remain understudied, most probably because the addition and presence of the modification is more easily studied than its removal and absence. Here, we report the identification of an uncharacterized protein tyrosine phosphatase PPH‐7 in C. elegans, a member of the evolutionary conserved PTPN family of phosphatases. Lack of PPH‐7 function led to reduction of fertility and embryonic lethality at elevated temperatures. Proteomics revealed changes in the regulation of targets of the von Hippel–Lindau (VHL) E3 ligase, suggesting a potential role for PPH‐7 in the regulation of VHL. Using long‐read sequencing, we identify the genetic lesion in a temperature‐sensitive C. elegans mutant. We find that a previously uncharacterized tyrosine phosphatase (PPH‐7) is required for spermatogenesis and embryonic development at elevated temperatures. Analysis of the proteome revealed that multiple known targets of the Von Hippel–Lindau tumor suppressor are downregulated in PPH‐7 deficient mutants.
ISSN:2211-5463
2211-5463
DOI:10.1002/2211-5463.13771