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.

Cellular Signalling
|August 6, 2025
PubMed

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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