Dataset Information

Novel non-canonical role of STAT1 in Natural Killer cell cytotoxicity

ABSTRACT: STAT1 is an important regulator of NK cell maturation and cytotoxicity. Although the consequences of Stat1-deficiency have been described in detail the underlying molecular functions of STAT1 in NK cells are only partially understood. Here we describe a novel non-canonical role of STAT1 that was unmasked in NK cells expressing Stat1-Y701F. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation and cytokine-induced transcriptional activity. As expected Stat1-Y701F mice displayed impaired NK cell maturation comparable to Stat1-/- animals. In contrast Stat1-Y701F NK cells exerted a significantly enhanced cytotoxicity in vitro and in vivo suggesting a so-far unknown cytoplasmic function. Using immunofluorescence technology we uncovered the recruitment of STAT1 to the immunological synapse during NK cell killing. A Stat1ind mouse expressing FLAG-tagged STAT1α was used to study the STAT1α interactome in NK cells. Mass spectrometry revealed that STAT1 directly binds proteins involved in cell junction formation and proteins associated to membrane or membrane-bound vesicles. We propose a novel function for STAT1 in the immunological synapse of NK cells regulating tumor surveillance and cytotoxicity.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Natural Killer Cell, Blood

SUBMITTER: Christopher Gerner

LAB HEAD: Christopher Gerner

PROVIDER: PXD002206 | Pride | 2016-10-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	NK_cells_1_stimulated_IP_STAT1.mgf	Mgf
	NK_cells_1_stimulated_IP_STAT1.mzid.gz	Mzid
	NK_cells_1_stimulated_IP_STAT1.pride.mgf.gz	Mgf
	NK_cells_1_stimulated_IP_STAT1.pride.mztab.gz	Mztab
	NK_cells_1_stimulated_IP_STAT1.raw	Raw

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Publications

Novel non-canonical role of STAT1 in Natural Killer cell cytotoxicity.

Putz Eva Maria EM Putz Eva Maria EM Majoros Andrea A Gotthardt Dagmar D Prchal-Murphy Michaela M Zebedin-Brandl Eva Maria EM Fux Daniela Alexandra DA Schlattl Andreas A Schreiber Robert D RD Carotta Sebastian S Müller Mathias M Gerner Christopher C Decker Thomas T Sexl Veronika V

Oncoimmunology 20160519 9

STAT1 is an important regulator of NK cell maturation and cytotoxicity. Although the consequences of <i>Stat1</i>-deficiency have been described in detail the underlying molecular functions of STAT1 in NK cells are only partially understood. Here, we describe a novel non-canonical role of STAT1 that was unmasked in NK cells expressing a <i>Stat1-Y701F</i> mutant. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation and cytokine-induced transcriptional activity a ...[more]

PMID: 27757297

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