Roles of unphosphorylated STATs in signaling.
Jinbo Yang,George R. Stark +1 more
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TLDR
The roles of U-STATs in transcription and regulation of gene expression are discussed, which are distinct from those used by phosphorylated STAT (P-STAT) dimers.Abstract:
The seven members of the signal transducer and activator of transcription (STAT) family of transcription factors are activated in response to many different cytokines and growth factors by phosphorylation of specific tyrosine residues. The STAT1 and STAT3 genes are specific targets of activated STATs 1 and 3, respectively, resulting in large increases in the levels of these unphosphorylated STATs (U-STATs) in response to the interferons (STAT1) or ligands that active gp130, such as IL-6 (STAT3). U-STATs drive gene expression by novel mechanisms distinct from those used by phosphorylated STAT (P-STAT) dimers. In this review, we discuss the roles of U-STATs in transcription and regulation of gene expression.read more
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Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells
Eunhee Kim,Mi-Suk Kim,Dong Hun Woo,Yongjae Shin,Jihye Shin,Nakho Chang,Young-Taek Oh,Hong Sug Kim,Jingeun Rheey,Ichiro Nakano,Cheolju Lee,Kyeung Min Joo,Jeremy N. Rich,Do-Hyun Nam,Jeongwu Lee +14 more
TL;DR: It is shown that EZH2 binds to and methylates STAT3, leading to enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3.
Journal ArticleDOI
Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors.
Kodappully Sivaraman Siveen,Sakshi Sikka,Rohit Surana,Xiaoyun Dai,Jingwen Zhang,Alan Prem Kumar,B. K. H. Tan,Gautam Sethi,Anupam Bishayee +8 more
TL;DR: The evidence for critical roles ofSTAT3 in oncogenesis is presented and the potential for development of novel cancer therapies based on mechanistic understanding of STAT3 signaling cascade is discussed.
Journal ArticleDOI
STAT3 Is Required for Proliferation and Maintenance of Multipotency in Glioblastoma Stem Cells
TL;DR: Treatment of putative glioblastoma stem cells with two chemically distinct small molecule inhibitors of STAT3 DNA‐binding inhibits cell proliferation and the formation of new neurospheres from single cells, suggesting that STAT3 regulates the growth and self‐renewal of GBM‐SCs and is thus a potential target for cancer stem cell‐directed therapy of gliOBlastoma multiforme.
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STAT3 signaling in immunity.
TL;DR: Information on the numerous and distinct biological actions of STAT3 is summarized, and recent discoveries are highlighted, with a specific focus on STAT3 function in the immune and hematopoietic systems.
Journal ArticleDOI
Interferons and viral infections.
Volker Fensterl,Ganes C. Sen +1 more
TL;DR: The effectiveness of theinterferon system in counteracting viral infections is reflected by the multitude of inhibitors of interferon induction or interferons action that are encoded by many viruses, preventing their eradication and resulting in the continued coexistence of viruses and vertebrates.
References
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Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
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How cells respond to interferons
TL;DR: The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interFERons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
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STATs and Gene Regulation
TL;DR: The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins.
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STATs: transcriptional control and biological impact
David E. Levy,James E. Darnell +1 more
TL;DR: The signal transducer and activator of transcription (STAT) proteins are among the most well studied of the latent cytoplasmic signal-dependent transcription-factor pathways.
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IFNγ, and lymphocytes prevent primary tumour development and shape tumour immunogenicity
Vijay Shankaran,Hiroaki Ikeda,Allen T. Bruce,J. Michael White,Paul E. Swanson,Lloyd J. Old,Robert D. Schreiber +6 more
TL;DR: It is shown that lymphocytes and IFNγ collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity, which explains the apparent paradox of tumour formation in immunologically intact individuals.