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

Awasthi, Nagendra; Liongue, Clifford; Ward, Alister C.

doi:10.1186/s13045-021-01214-y

Journal of Hematology & Oncology

Table 2 Canonical and non-canonical functions of different STAT proteins

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

Functional modality	STAT protein	Examples	References
Inducible transcriptional activation	STAT1 and STAT2	Type I IFN stimulated pSTAT1/pSTAT2/IRF9 leads to transcription of IFN-stimulated genes (ISGs) that provide protection against viral infection	[64, 65]
	STAT3	IL-6 stimulated pSTAT3 leads to transcription of IL21 and other genes essential for Th17 cell differentiation	[66]
	STAT4	IL-12 stimulated pSTAT4 leads to transcription of NFKB1, CASP8 and other genes that impact neutrophil function	[12, 67]
	STAT5	EPO stimulated pSTAT5 leads to transcription of genes like GATA1, KLF1 and BCL2 that are essential for erythropoiesis	[68]
	STAT6	IL-4 stimulated STAT6 leads to transcription of genes like IL4, GATA3, IL1R11, HIPK2 and NFIL that are responsible for Th2 cell differentiation	[69]
Inducible transcriptional repression	STAT5	IL-7 stimulated pSTAT5 leads to repression of IGK that suppresses immunoglobulin gene rearrangement	[70]
Inducible transcriptional repression	STAT6	IL-4 stimulated pSTAT6 leads to repression of genes like NLRP3 and IL1B, facilitating alternative macrophage polarization	[71]
Basal transcriptional activation	STAT1	uSTAT1/IRF1 heterodimer mediates transcription of LMP2	[57]
	STAT1 and STAT2	uSTAT1/uSTAT2/IRF9 mediates prolonged transcription of IFN-responsive genes	[18]
	STAT3	uSTAT3/uNFκB mediates transcription of RANTES, IL6, IL8, MET and MRSA	[72, 73]
Basal transcriptional repression	STAT5	uSTAT5/CTCF complex represses expression of genes involved in megakaryocytic differentiation	[58, 74]
Inducible non-nuclear functions	STAT3	IL-6 stimulated pSTAT3 alters Ca2 + levels and membrane potential in mitochondria to influence effector functions of CD4 + T-cells	[75]
Inducible non-nuclear functions	STAT5	IL-2 stimulated pSTAT5 regulates mitochondrial gene expression	[76]
Basal non-nuclear functions	STAT1	uSTAT1 functions at immunological synapses in NK cells to impact cytotoxicity	[77]
	STAT3	uSTAT3 sequesters FoxO transcription factors within cytoplasm that extends T cell activation	[78]
	STAT5	uSTAT5 maintains structural integrity of endoplasmic reticulum, Golgi body and mitochondria	[79]

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ISSN: 1756-8722

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