A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation
The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induc...
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| Veröffentlicht in: | Genes and immunity 2020-02, Vol.21 (2), p.136-141 |
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| creator | Chehboun, Salma Leiva-Torres, Gabriel André Charbonneau, Benoît Eveleigh, Robert Bourque, Guillaume Vidal, Silvia Marina |
| description | The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induced W484G mutation in the
Stat5a
gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from
Stat5a
mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of
Stat5a
mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that
Stat5a
mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. Overall, our results demonstrate that the W484G mutation in the linker domain of STAT5A is sufficient to compromise STAT5A function in NK-cell homeostasis, responsiveness, and tumoricidal function. |
| doi_str_mv | 10.1038/s41435-019-0088-6 |
| format | Article |
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Stat5a
gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from
Stat5a
mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of
Stat5a
mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that
Stat5a
mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. Overall, our results demonstrate that the W484G mutation in the linker domain of STAT5A is sufficient to compromise STAT5A function in NK-cell homeostasis, responsiveness, and tumoricidal function.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/s41435-019-0088-6</identifier><identifier>PMID: 31591503</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/2 ; 13/21 ; 13/95 ; 38/22 ; 38/23 ; 38/70 ; 631/208/248 ; 631/250/2504 ; 64/60 ; 82/80 ; Analysis ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Brief Communication ; Cancer Research ; Cell number ; Cell Proliferation - genetics ; Cell survival ; Cell Survival - genetics ; Cellular immunity ; Cytotoxicity ; DNA-Binding Proteins - genetics ; Female ; Gene Expression ; Gene mutations ; Gene regulation ; Granzyme B ; Homeostasis ; Human Genetics ; Immunology ; Influence ; Interleukin 15 ; Killer cells ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mutants ; Mutation ; Point Mutation ; Signal Transduction - genetics ; STAT proteins ; Stat5 protein ; STAT5 Transcription Factor - genetics ; STAT5 Transcription Factor - immunology ; STAT5 Transcription Factor - metabolism ; Structure ; TOR protein ; Trans-Activators - genetics ; γ-Interferon</subject><ispartof>Genes and immunity, 2020-02, Vol.21 (2), p.136-141</ispartof><rights>Springer Nature Limited 2019</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>Springer Nature Limited 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-8acb089941196fc4fc60011c8a15a90d3d40251d1cfef2e11cce6223a71397ea3</citedby><cites>FETCH-LOGICAL-c473t-8acb089941196fc4fc60011c8a15a90d3d40251d1cfef2e11cce6223a71397ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31591503$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chehboun, Salma</creatorcontrib><creatorcontrib>Leiva-Torres, Gabriel André</creatorcontrib><creatorcontrib>Charbonneau, Benoît</creatorcontrib><creatorcontrib>Eveleigh, Robert</creatorcontrib><creatorcontrib>Bourque, Guillaume</creatorcontrib><creatorcontrib>Vidal, Silvia Marina</creatorcontrib><title>A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induced W484G mutation in the
Stat5a
gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from
Stat5a
mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of
Stat5a
mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that
Stat5a
mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. 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genetics</topic><topic>Cell survival</topic><topic>Cell Survival - genetics</topic><topic>Cellular immunity</topic><topic>Cytotoxicity</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gene mutations</topic><topic>Gene regulation</topic><topic>Granzyme B</topic><topic>Homeostasis</topic><topic>Human Genetics</topic><topic>Immunology</topic><topic>Influence</topic><topic>Interleukin 15</topic><topic>Killer cells</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Point Mutation</topic><topic>Signal Transduction - genetics</topic><topic>STAT proteins</topic><topic>Stat5 protein</topic><topic>STAT5 Transcription Factor - genetics</topic><topic>STAT5 Transcription Factor - immunology</topic><topic>STAT5 Transcription Factor - metabolism</topic><topic>Structure</topic><topic>TOR protein</topic><topic>Trans-Activators - genetics</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chehboun, Salma</creatorcontrib><creatorcontrib>Leiva-Torres, Gabriel André</creatorcontrib><creatorcontrib>Charbonneau, Benoît</creatorcontrib><creatorcontrib>Eveleigh, Robert</creatorcontrib><creatorcontrib>Bourque, Guillaume</creatorcontrib><creatorcontrib>Vidal, Silvia Marina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chehboun, Salma</au><au>Leiva-Torres, Gabriel André</au><au>Charbonneau, Benoît</au><au>Eveleigh, Robert</au><au>Bourque, Guillaume</au><au>Vidal, Silvia Marina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>21</volume><issue>2</issue><spage>136</spage><epage>141</epage><pages>136-141</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><abstract>The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induced W484G mutation in the
Stat5a
gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from
Stat5a
mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of
Stat5a
mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that
Stat5a
mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. Overall, our results demonstrate that the W484G mutation in the linker domain of STAT5A is sufficient to compromise STAT5A function in NK-cell homeostasis, responsiveness, and tumoricidal function.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31591503</pmid><doi>10.1038/s41435-019-0088-6</doi><tpages>6</tpages></addata></record> |
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| subjects | 13/1 13/2 13/21 13/95 38/22 38/23 38/70 631/208/248 631/250/2504 64/60 82/80 Analysis Animals Biomedical and Life Sciences Biomedicine Brief Communication Cancer Research Cell number Cell Proliferation - genetics Cell survival Cell Survival - genetics Cellular immunity Cytotoxicity DNA-Binding Proteins - genetics Female Gene Expression Gene mutations Gene regulation Granzyme B Homeostasis Human Genetics Immunology Influence Interleukin 15 Killer cells Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Male Mice Mice, Inbred C57BL Mutants Mutation Point Mutation Signal Transduction - genetics STAT proteins Stat5 protein STAT5 Transcription Factor - genetics STAT5 Transcription Factor - immunology STAT5 Transcription Factor - metabolism Structure TOR protein Trans-Activators - genetics γ-Interferon |
| title | A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation |
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