CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance
The transcription factor STAT1 is important in natural killer (NK) cells, which provide immediate defense against tumor and virally infected cells. We show that mutation of a single phosphorylation site (Stat1-S727A) enhances NK cell cytotoxicity against a range of tumor cells, accompanied by increa...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713003598 |
| _version_ | 1828416721341382656 |
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| author | Eva Maria Putz Dagmar Gotthardt Gregor Hoermann Agnes Csiszar Silvia Wirth Angelika Berger Elisabeth Straka Doris Rigler Barbara Wallner Amanda M. Jamieson Winfried F. Pickl Eva Maria Zebedin-Brandl Mathias Müller Thomas Decker Veronika Sexl |
| author_facet | Eva Maria Putz Dagmar Gotthardt Gregor Hoermann Agnes Csiszar Silvia Wirth Angelika Berger Elisabeth Straka Doris Rigler Barbara Wallner Amanda M. Jamieson Winfried F. Pickl Eva Maria Zebedin-Brandl Mathias Müller Thomas Decker Veronika Sexl |
| author_sort | Eva Maria Putz |
| collection | DOAJ |
| description | The transcription factor STAT1 is important in natural killer (NK) cells, which provide immediate defense against tumor and virally infected cells. We show that mutation of a single phosphorylation site (Stat1-S727A) enhances NK cell cytotoxicity against a range of tumor cells, accompanied by increased expression of perforin and granzyme B. Stat1-S727A mice display significantly delayed disease onset in NK cell-surveilled tumor models including melanoma, leukemia, and metastasizing breast cancer. Constitutive phosphorylation of S727 depends on cyclin-dependent kinase 8 (CDK8). Inhibition of CDK8-mediated STAT1-S727 phosphorylation may thus represent a therapeutic strategy for stimulating NK cell-mediated tumor surveillance. |
| first_indexed | 2024-12-10T14:07:29Z |
| format | Article |
| id | doaj.art-5dbfdc32240242eeb0c34a9291efed38 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T14:07:29Z |
| publishDate | 2013-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5dbfdc32240242eeb0c34a9291efed382022-12-22T01:45:36ZengElsevierCell Reports2211-12472013-08-014343744410.1016/j.celrep.2013.07.012CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor SurveillanceEva Maria Putz0Dagmar Gotthardt1Gregor Hoermann2Agnes Csiszar3Silvia Wirth4Angelika Berger5Elisabeth Straka6Doris Rigler7Barbara Wallner8Amanda M. Jamieson9Winfried F. Pickl10Eva Maria Zebedin-Brandl11Mathias Müller12Thomas Decker13Veronika Sexl14Institute of Pharmacology and Toxicology, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaInstitute of Pharmacology and Toxicology, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, AustriaResearch Institute of Molecular Pathology, 1030 Vienna, AustriaResearch Institute of Molecular Pathology, 1030 Vienna, AustriaInstitute of Pharmacology and Toxicology, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaInstitute of Pharmacology and Toxicology, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaInstitute of Animal Breeding and Genetics, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaInstitute of Animal Breeding and Genetics, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaMax F. Perutz Laboratories, University of Vienna, 1030 Vienna, AustriaInstitute of Immunology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Animal Breeding and Genetics, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaMax F. Perutz Laboratories, University of Vienna, 1030 Vienna, AustriaInstitute of Pharmacology and Toxicology, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaThe transcription factor STAT1 is important in natural killer (NK) cells, which provide immediate defense against tumor and virally infected cells. We show that mutation of a single phosphorylation site (Stat1-S727A) enhances NK cell cytotoxicity against a range of tumor cells, accompanied by increased expression of perforin and granzyme B. Stat1-S727A mice display significantly delayed disease onset in NK cell-surveilled tumor models including melanoma, leukemia, and metastasizing breast cancer. Constitutive phosphorylation of S727 depends on cyclin-dependent kinase 8 (CDK8). Inhibition of CDK8-mediated STAT1-S727 phosphorylation may thus represent a therapeutic strategy for stimulating NK cell-mediated tumor surveillance.http://www.sciencedirect.com/science/article/pii/S2211124713003598 |
| spellingShingle | Eva Maria Putz Dagmar Gotthardt Gregor Hoermann Agnes Csiszar Silvia Wirth Angelika Berger Elisabeth Straka Doris Rigler Barbara Wallner Amanda M. Jamieson Winfried F. Pickl Eva Maria Zebedin-Brandl Mathias Müller Thomas Decker Veronika Sexl CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance Cell Reports |
| title | CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance |
| title_full | CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance |
| title_fullStr | CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance |
| title_full_unstemmed | CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance |
| title_short | CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance |
| title_sort | cdk8 mediated stat1 s727 phosphorylation restrains nk cell cytotoxicity and tumor surveillance |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713003598 |
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