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

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Version 2 2024-06-19, 07:06
Version 1 2021-11-26, 08:19
journal contribution
posted on 2024-06-19, 07:06 authored by N Awasthi, Clifford LiongueClifford Liongue, Alister WardAlister Ward
AbstractSTAT 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.

History

Journal

Journal of Hematology and Oncology

Volume

14

Article number

ARTN 198

Pagination

1 - 17

Location

England

Open access

  • Yes

ISSN

1756-8722

eISSN

1756-8722

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

1

Publisher

BMC