TY  - JOUR
A1  - Freund, Patricia
A1  - Kerenyi, Marc
A1  - Hager, Matthias
A1  - Wagner, Tanja
A1  - Wingelhofer, Bettina
A1  - Ha, Pham
A1  - Elabd, Mohamed
A1  - Han, Xiaonan
A1  - Valent, Peter
A1  - Gouilleux, Fabrice
A1  - Sexl, Veronika
A1  - Krämer, Oliver Holger
A1  - Groner, Bernd
A1  - Moriggl, Richard
T1  - O-GlcNAcylation of STAT5 controls tyrosine phosphorylation and oncogenic transcription in STAT5-dependent malignancies
T2  - Leukemia
N2  - 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.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44706
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-447067
SN  - 1476-5551
SN  - 0887-6924
N1  - 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/
VL  - 31
IS  - 10
SP  - 2132
EP  - 2142
PB  - Springer Nature
CY  - London
ER  -