IMR Press / FBL / Volume 13 / Issue 16 / DOI: 10.2741/3151

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
The different functions of Stat5 and chromatin alteration through Stat5 proteins
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1 Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria
2 Max F. Perutz Laboratories, Department of Medical Biochemistry, Division of Molecular Biology, Medical University of Vienna, Vienna, Austria
3 Institute of Molecular Pathology, Vienna Biocenter (VBC), Vienna, Austria
4 Department of Pharmacology, Medical University of Vienna
5 Institute of Animal Breeding and Genetics, Veterinary University of Vienna, Vienna, Austria
6 Institute of Clinical Pathology, Medical University of Vienna
7 Institut National de la Santé et de la Recherche Médicale (EMI 351), Amiens, France
8 Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Academic Editor:Kevin Bunting
Front. Biosci. (Landmark Ed) 2008, 13(16), 6237–6254; https://doi.org/10.2741/3151
Published: 1 May 2008
(This article belongs to the Special Issue JAKSTAT signaling in hematopoiesis)
Abstract

Stat5 proteins modulate gene transcription upon cytokine- and growth factor action. Stat5a and Stat5b proteins alone are weak activators of transcription. They can modify chromatin organization through oligomerization and they act predominantly in co-operation and interaction with other proteins. The conservative view of exclusively nuclear functions of Stat5 was challenged by the observation of additional Stat5 effects in the cytoplasm, resulting in activation of the PI3K-Akt pathway. We summarize biological consequences of mutations in conserved domains of Stat5 or of deletions in the N- or C-terminal domains with impact on target gene transcription. Formation of higher-order oligomers is dramatically changed upon amino- or carboxyterminal deletions in Stat5 proteins. Mutations in or deletion of the Stat5 N-terminus leads to diminished leukemogenic potential of oncogenic Stat5, probably due to the inability to form Stat5 tetramers. The Stat5 N-terminal domain prevents persistent activation and can act as a DNA-docking platform for the glucocorticoid receptor (GR). The corresponding protocols should facilitate follow-up studies on Stat5 proteins and their contribution to normal physiological versus pathological processes through differential chromatin binding.

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