O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies

  • The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. The lack of O-GlcNAcylation diminished phospho-ERK and phospho-AKT levels. Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. O-GlcNAcylation of STAT5 could be required for nutrient sensing and metabolism of cancer cells.
Metadaten
Author:Patricia Freund, Marc Kerenyi, Matthias Hager, Tanja Wagner, Bettina Wingelhofer, Pham Ha, Mohamed Elabd, Xiaonan Han, Peter Valent, Fabrice Gouilleux, Veronika Sexl, Oliver Holger Krämer, Bernd GronerGND, Richard Moriggl
URN:urn:nbn:de:hebis:30:3-447067
DOI:https://doi.org/10.1038/leu.2017.4
ISSN:1476-5551
ISSN:0887-6924
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28074064
Parent Title (English):Leukemia
Publisher:Springer Nature
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2017/11/02
Date of first Publication:2017/02/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/11/02
Volume:31
Issue:10
Page Number:11
First Page:2132
Last Page:2142
Note:
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
HeBIS-PPN:425322726
Institutes:Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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