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

Eva Maria Putz, Andrea Majoros, Dagmar Gotthardt, Michaela Prchal-Murphy, Eva Maria Zebedin-Brandl, Daniela Alexandra Fux, Andreas Schlattl, Robert D. Schreiber, Sebastian Carotta, Mathias Müller, Christopher Gerner, Thomas Decker, Veronika Sexl

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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 a Stat1-Y701F mutant. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation and cytokine-induced transcriptional activity as verified by RNA-seq analysis. 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 compared to Stat1−/− NK cells in the absence of detectable transcriptional activity. We thus investigated the STAT1 interactome using primary NK cells derived from Stat1ind mice that inducibly express a FLAG-tagged STAT1. Mass spectrometry revealed that STAT1 directly binds proteins involved in cell junction formation and proteins associated to membrane or membrane-bound vesicles. In line, immunofluorescence studies uncovered the recruitment of STAT1 to the target-cell interphase during NK cell killing. This led us to propose a novel function for STAT1 at the immunological synapse in NK cells regulating tumor surveillance and cytotoxicity.

Original languageEnglish
Article numbere1186314
Issue number9
StatePublished - Sep 1 2016


  • Interactome; NK cell
  • STAT1
  • tumor surveillance
  • vesicle


Dive into the research topics of 'Novel non-canonical role of STAT1 in Natural Killer cell cytotoxicity'. Together they form a unique fingerprint.

Cite this