ward-statproteins-2021.pdf (2.68 MB)
STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer
journal contribution
posted on 2021-01-01, 00:00 authored by N Awasthi, Clifford LiongueClifford Liongue, Alister WardAlister WardAbstractSTAT 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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Journal of Hematology and OncologyVolume
14Issue
1Article number
ARTN 198Pagination
1 - 17Publisher
BMCLocation
London, Eng.Publisher DOI
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1756-8722eISSN
1756-8722Language
EnglishPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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