Cited by 1,201Cytokine Signaling Pathways and InteractionsProtein Tyrosine PhosphatasesNF-κB Signaling Pathways

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The role of STATs in transcriptional control and their impact on cellular function

Bromberg, Jacqueline, Darnell, James E·2000·Oncogene

DOI 10.1038/sj.onc.1203476

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Abstract

The STAT proteins (Signal Transducers and Activators of Transcription), were identified in the last decade as transcription factors which were critical in mediating virtually all cytokine driven signaling. These proteins are latent in the cytoplasm and become activated through tyrosine phosphorylation which typically occurs through cytokine receptor associated kinases (JAKs) or growth factor receptor tyrosine kinases. Recently a number of non-receptor tyrosine kinases (for example src and abl) have been found to cause STAT phosphorylation. Phosphorylated STATs form homo- or hetero-dimers, enter the nucleus and working coordinately with other transcriptional co-activators or transcription factors lead to increased transcriptional initiation. In normal cells and in animals, ligand dependent activation of the STATs is a transient process, lasting for several minutes to several hours. In contrast, in many cancerous cell lines and tumors, where growth factor dysregulation is frequently at the heart of cellular transformation, the STAT proteins (in particular Stats 1, 3 and 5) are persistently tyrosine phosphorylated or activated. The importance of STAT activation to growth control in experiments using anti-sense molecules or dominant negative STAT protein encoding constructs performed in cell lines or studies in animals lacking specific STATs strongly indicate that STATs play an important role in controlling cell cycle progression and apoptosis. Stat1 plays an important role in growth arrest, in promoting apoptosis and is implicated as a tumor suppressor; while Stats 3 and 5 are involved in promoting cell cycle progression and cellular transformation and preventing apoptosis. Many questions remain including: (1) a better understanding of how the STAT proteins through association with other factors increase transcription initiation; (2) a more complete definition of the sets of genes which are activated by different STATs and (3) how these sets of activated genes differ as a function of cell type. Finally, in the context of many cancers, where STATs are frequently persistently activated, an understanding of the mechanisms leading to their constitutive activation and defining the potential importance of persistent STAT activation in human tumorigenesis remains. Oncogene (2000).

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Authors: Bromberg, J., & Darnell, J. E.
Affiliations: Rockefeller University (US)
ORCID: Bromberg, Jacqueline
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2000-05-25
Volume: 19
Issue: 21
Pages: 2468-2473
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1203476
OpenAlex: W1977681992
Cited by: 1,201
References: 66
Citations by year: 2026: 10 · 2025: 22 · 2024: 21 · 2023: 24 · 2022: 37 · 2021: 40 · 2020: 46 · 2019: 41 · 2018: 42 · 2017: 51 · 2016: 46 · 2015: 49 · 2014: 59 · 2013: 67 · 2012: 56
FWCI: 6.32
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: STAT proteins, transcriptional regulation, cytokine signaling, JAK kinases, tyrosine phosphorylation, STAT1, STAT3, STAT5, cell cycle progression, apoptosis, tumor suppressor, cell transformation, carcinogenesis, transcriptional coactivator
MeSH terms: Animals, Cell Division, Cell Transformation, Neoplastic, DNA-Binding Proteins, Gene Expression Regulation, Humans, Milk Proteins, Neoplasms, Structure-Activity Relationship, Transcription, Genetic, Trans-Activators, STAT1 Transcription Factor, STAT3 Transcription Factor, STAT5 Transcription Factor

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The role of STATs in transcriptional control and their impact on cellular function

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