Targeting the transcriptional activity of STAT3 by a novel fusion protein

  • BMC Cancer. 2022 Jul 10;22(1):751. doi: 10.1186/s12885-022-09837-1.
Yanqiong Chen  1  2 ,  Wenting Zhang  1 ,  Xiufeng Bai  3  4 ,  Yi Liu  5  6
Affiliations
  • 1. National Clinical Research Center for Geriatrics and Laboratory of Human Disease and Immunotherapies, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China.
  • 2. Research Institute of Inflammation and Immunology (RIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
  • 3. National Clinical Research Center for Geriatrics and Laboratory of Human Disease and Immunotherapies, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China. [email protected].
  • 4. Research Institute of Inflammation and Immunology (RIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. [email protected].
  • 5. Research Institute of Inflammation and Immunology (RIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. [email protected].
  • 6. Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, 610041, China. [email protected].
PMID: 35810312 DOI: 10.1186/s12885-022-09837-1
Abstract

Background: The continuous activation of transcription factors drives many diseases, including tumors, autoimmune disease, neurodegenerative disease, and male infertility. Thus, Blocking the transcriptional activity of these proteins may inhibit disease progression. In this study, we developed a new method to specifically inhibit the activity of the transcription factor STAT3.

Methods: Fusing the transcriptional inhibitory domain KRAB with STAT3 successfully blocked the transcription activity of STAT3 in Cancer cells without affecting its function in the mitochondria and lysosomes.

Results: the expression of KRAB-STAT3 fusion protein inhibited the growth of tumor cells.

Conclusions: The KRAB-STAT3 fusion protein provides a novel approach for drug development for the treatment of Cancer or autoimmune diseases.

Keywords
Autoimmune diseases; KRAB; Male infertility; Neurodegenerative diseases; STAT3; Transcription; cancer.
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