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STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer

STAT proteins represent an important family of evolutionarily conserved transcription factors that play key roles in diverse biological processes, notably including blood and immune cell development and function. Classically, STAT proteins have been viewed as inducible activators of transcription th...

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Detalles Bibliográficos
Autores principales: Awasthi, Nagendra, Liongue, Clifford, Ward, Alister C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607625/
https://www.ncbi.nlm.nih.gov/pubmed/34809691
http://dx.doi.org/10.1186/s13045-021-01214-y
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author Awasthi, Nagendra
Liongue, Clifford
Ward, Alister C.
author_facet Awasthi, Nagendra
Liongue, Clifford
Ward, Alister C.
author_sort Awasthi, Nagendra
collection PubMed
description STAT proteins represent an important family of evolutionarily conserved transcription factors that play key roles in diverse biological processes, notably including blood and immune cell development and function. Classically, STAT proteins have been viewed as inducible activators of transcription that mediate cellular responses to extracellular signals, particularly cytokines. In this ‘canonical’ paradigm, latent STAT proteins become tyrosine phosphorylated following receptor activation, typically via downstream JAK proteins, facilitating their dimerization and translocation into the nucleus where they bind to specific sequences in the regulatory region of target genes to activate transcription. However, growing evidence has challenged this paradigm and identified alternate ‘non-canonical’ functions, such as transcriptional repression and roles outside the nucleus, with both phosphorylated and unphosphorylated STATs involved. This review provides a revised framework for understanding the diverse kaleidoscope of STAT protein functional modalities. It further discusses the implications of this framework for our understanding of STAT proteins in normal blood and immune cell biology and diseases such as cancer, and also provides an evolutionary context to place the origins of these alternative functional modalities.
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spelling pubmed-86076252021-11-22 STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer Awasthi, Nagendra Liongue, Clifford Ward, Alister C. J Hematol Oncol Review STAT proteins represent an important family of evolutionarily conserved transcription factors that play key roles in diverse biological processes, notably including blood and immune cell development and function. Classically, STAT proteins have been viewed as inducible activators of transcription that mediate cellular responses to extracellular signals, particularly cytokines. In this ‘canonical’ paradigm, latent STAT proteins become tyrosine phosphorylated following receptor activation, typically via downstream JAK proteins, facilitating their dimerization and translocation into the nucleus where they bind to specific sequences in the regulatory region of target genes to activate transcription. However, growing evidence has challenged this paradigm and identified alternate ‘non-canonical’ functions, such as transcriptional repression and roles outside the nucleus, with both phosphorylated and unphosphorylated STATs involved. This review provides a revised framework for understanding the diverse kaleidoscope of STAT protein functional modalities. It further discusses the implications of this framework for our understanding of STAT proteins in normal blood and immune cell biology and diseases such as cancer, and also provides an evolutionary context to place the origins of these alternative functional modalities. BioMed Central 2021-11-22 /pmc/articles/PMC8607625/ /pubmed/34809691 http://dx.doi.org/10.1186/s13045-021-01214-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Awasthi, Nagendra
Liongue, Clifford
Ward, Alister C.
STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
title STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
title_full STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
title_fullStr STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
title_full_unstemmed STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
title_short STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
title_sort stat proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607625/
https://www.ncbi.nlm.nih.gov/pubmed/34809691
http://dx.doi.org/10.1186/s13045-021-01214-y
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