通过新型融合蛋白靶向 STAT3 的转录活性。
Targeting the transcriptional activity of STAT3 by a novel fusion protein.
机构信息
National Clinical Research Center for Geriatrics and Laboratory of Human Disease and Immunotherapies, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China.
Research Institute of Inflammation and Immunology (RIII), Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
出版信息
BMC Cancer. 2022 Jul 10;22(1):751. doi: 10.1186/s12885-022-09837-1.
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.
背景
转录因子的持续激活导致许多疾病，包括肿瘤、自身免疫性疾病、神经退行性疾病和男性不育。因此，阻断这些蛋白质的转录活性可能会抑制疾病的进展。在这项研究中，我们开发了一种新的方法来特异性抑制转录因子 STAT3 的活性。
方法
将转录抑制结构域 KRAB 与 STAT3 融合，成功地阻断了 STAT3 在癌细胞中的转录活性，而不影响其在线粒体和溶酶体中的功能。
结果
KRAB-STAT3 融合蛋白的表达抑制了肿瘤细胞的生长。
结论
KRAB-STAT3 融合蛋白为治疗癌症或自身免疫性疾病的药物开发提供了一种新的方法。
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