دورية أكاديمية
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Ubiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast wtf meiotic drivers.

التفاصيل البيبلوغرافية
العنوان: Ubiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast wtf meiotic drivers.
المؤلفون: Zheng JX; National Institute of Biological Sciences, Beijing, 102206, China.; Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China., Du TY; National Institute of Biological Sciences, Beijing, 102206, China.; College of Life Sciences, Beijing Normal University, Beijing, 100875, China., Shao GC; National Institute of Biological Sciences, Beijing, 102206, China., Ma ZH; National Institute of Biological Sciences, Beijing, 102206, China., Jiang ZD; National Institute of Biological Sciences, Beijing, 102206, China., Hu W; National Institute of Biological Sciences, Beijing, 102206, China., Suo F; National Institute of Biological Sciences, Beijing, 102206, China., He W; National Institute of Biological Sciences, Beijing, 102206, China., Dong MQ; National Institute of Biological Sciences, Beijing, 102206, China.; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China., Du LL; National Institute of Biological Sciences, Beijing, 102206, China. dulilin@nibs.ac.cn.; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China. dulilin@nibs.ac.cn.
المصدر: Nature communications [Nat Commun] 2023 Dec 14; Vol. 14 (1), pp. 8334. Date of Electronic Publication: 2023 Dec 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Schizosaccharomyces*/genetics , Schizosaccharomyces*/metabolism, Antidotes ; Ubiquitination ; Golgi Apparatus/metabolism ; Ubiquitin/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; Ubiquitin-Protein Ligases/metabolism
مستخلص: Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in eukaryotes, the molecular mechanisms behind their selfish behavior are poorly understood. In several fission yeast species, single-gene KMDs belonging to the wtf gene family exert selfish killing by expressing a toxin and an antidote through alternative transcription initiation. Here we investigate how the toxin and antidote products of a wtf-family KMD gene can act antagonistically. Both the toxin and the antidote are multi-transmembrane proteins, differing only in their N-terminal cytosolic tails. We find that the antidote employs PY motifs (Leu/Pro-Pro-X-Tyr) in its N-terminal cytosolic tail to bind Rsp5/NEDD4 family ubiquitin ligases, which ubiquitinate the antidote. Mutating PY motifs or attaching a deubiquitinating enzyme transforms the antidote into a toxic protein. Ubiquitination promotes the transport of the antidote from the trans-Golgi network to the endosome, thereby preventing it from causing toxicity. A physical interaction between the antidote and the toxin enables the ubiquitinated antidote to translocate the toxin to the endosome and neutralize its toxicity. We propose that post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs.
(© 2023. The Author(s).)
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المشرفين على المادة: 0 (Antidotes)
0 (Ubiquitin)
0 (Endosomal Sorting Complexes Required for Transport)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
تواريخ الأحداث: Date Created: 20231214 Date Completed: 20231216 Latest Revision: 20231217
رمز التحديث: 20231218
مُعرف محوري في PubMed: PMC10721834
DOI: 10.1038/s41467-023-44151-9
PMID: 38097609
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-44151-9