A STAT3 protein complex required for mitochondrial mRNA stability and cancer
Summary: Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723010446 |
| _version_ | 1797687673528254464 |
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| author | C. Dilanka Fernando W. Samantha N. Jayasekara Chaitanya Inampudi Maija R.J. Kohonen-Corish Wendy A. Cooper Traude H. Beilharz Tracy M. Josephs Daniel J. Garama Daniel J. Gough |
| author_facet | C. Dilanka Fernando W. Samantha N. Jayasekara Chaitanya Inampudi Maija R.J. Kohonen-Corish Wendy A. Cooper Traude H. Beilharz Tracy M. Josephs Daniel J. Garama Daniel J. Gough |
| author_sort | C. Dilanka Fernando |
| collection | DOAJ |
| description | Summary: Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3. |
| first_indexed | 2024-03-12T01:21:06Z |
| format | Article |
| id | doaj.art-0b416294b8d648a2b18c0473e3703a04 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T01:21:06Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-0b416294b8d648a2b18c0473e3703a042023-09-13T04:24:58ZengElsevierCell Reports2211-12472023-09-01429113033A STAT3 protein complex required for mitochondrial mRNA stability and cancerC. Dilanka Fernando0W. Samantha N. Jayasekara1Chaitanya Inampudi2Maija R.J. Kohonen-Corish3Wendy A. Cooper4Traude H. Beilharz5Tracy M. Josephs6Daniel J. Garama7Daniel J. Gough8Department of Molecular Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia; Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaDepartment of Molecular Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia; Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaDepartment of Molecular Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia; Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, AustraliaGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; Woolcock Institute of Medical Research, Glebe, NSW 2037, Australia; School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; Faculty of Science, UTS Sydney, Ultimo, NSW 2007, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia; Sydney Medical School, University of Sydney, Camperdown, NSW 2006, AustraliaDevelopment and Stem Cells Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia; ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, AustraliaDepartment of Molecular Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia; Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia; Corresponding authorDepartment of Molecular Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia; Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia; Corresponding authorSummary: Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3.http://www.sciencedirect.com/science/article/pii/S2211124723010446CP: CancerCP: Molecular biology |
| spellingShingle | C. Dilanka Fernando W. Samantha N. Jayasekara Chaitanya Inampudi Maija R.J. Kohonen-Corish Wendy A. Cooper Traude H. Beilharz Tracy M. Josephs Daniel J. Garama Daniel J. Gough A STAT3 protein complex required for mitochondrial mRNA stability and cancer Cell Reports CP: Cancer CP: Molecular biology |
| title | A STAT3 protein complex required for mitochondrial mRNA stability and cancer |
| title_full | A STAT3 protein complex required for mitochondrial mRNA stability and cancer |
| title_fullStr | A STAT3 protein complex required for mitochondrial mRNA stability and cancer |
| title_full_unstemmed | A STAT3 protein complex required for mitochondrial mRNA stability and cancer |
| title_short | A STAT3 protein complex required for mitochondrial mRNA stability and cancer |
| title_sort | stat3 protein complex required for mitochondrial mrna stability and cancer |
| topic | CP: Cancer CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723010446 |
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