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Published on: October 9, 2016
Post-translational modifications of Stat3: The state of the art
Jiaxu Chen1, Caiyun Mao1, Ning Han1
1Department of Pharmacology, Heilongjiang University of Chinese Medicine, Harbin, China.
Abstract:
Signal transducer and activator of transcription 3 (Stat3), a critical transcription factor, plays an essential role in cellular processes such as proliferation, development, and differentiation. It also significantly contributes to the pathogenesis of cardiovascular diseases and various cancers, including breast cancer, pancreatic cancer, and renal cell carcinoma. The functional dynamics of Stat3 are intricately regulated by post-translational modifications (PTMs) such as phosphorylation, sulfenylation, acetylation, sulfhydrylation, and SUMOylation. These modifications, triggered by pathophysiological signals, induce structural changes in Stat3 across different cell types, thereby regulating distinct gene expression programs. Such modifications can either enhance or inhibit Stat3's transcriptional activity and affect its DNA-binding stability. This review explores the various PTMs that modulate Stat3 function, offering a comprehensive analysis of the regulatory mechanisms that govern Stat3 within cellular signaling networks. The findings are expected to provide valuable insights into the development of novel therapeutic agents targeting these pathways, ultimately revealing new targets and innovative strategies for treating a range of diseases.
Insights
Signal transducer and activator of transcription 3 (Stat3) is vital for cell functions and disease development. Its activity is precisely controlled by various post-translational modifications (PTMs), offering new therapeutic targets.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Biochemistry
Background:
- Signal transducer and activator of transcription 3 (Stat3) is a key transcription factor involved in cell proliferation, differentiation, and development.
- Dysregulated Stat3 activity is implicated in the pathogenesis of cardiovascular diseases and various cancers, including breast, pancreatic, and renal cell carcinoma.
Purpose of the Study:
- To review the diverse post-translational modifications (PTMs) that regulate Signal transducer and activator of transcription 3 (Stat3) function.
- To provide a comprehensive analysis of the regulatory mechanisms governing Stat3 within cellular signaling networks.
- To highlight the potential of Stat3-targeting pathways for novel therapeutic strategies.
Main Methods:
- Literature review of existing research on Stat3.
- Analysis of various post-translational modifications (PTMs) affecting Stat3.
- Exploration of Stat3's role in disease pathogenesis and cellular signaling.
Main Results:
- Stat3 function is modulated by multiple PTMs, including phosphorylation, sulfenylation, acetylation, sulfhydrylation, and SUMOylation.
- These modifications induce structural changes in Stat3, altering its transcriptional activity and DNA-binding stability.
- Pathophysiological signals trigger PTMs, leading to distinct gene expression programs in different cell types.
Conclusions:
- Post-translational modifications are critical regulators of Signal transducer and activator of transcription 3 (Stat3) activity.
- Understanding these regulatory mechanisms provides insights into Stat3's role in disease.
- Targeting Stat3 PTMs presents a promising avenue for developing innovative therapeutic strategies for cancer and cardiovascular diseases.
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