受体相互作用蛋白激酶1调节癌症进展和免疫反应的研究现状

doi:10.3969/j.issn.1674-8115.2024.06.015

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (6): 788-794.doi: 10.3969/j.issn.1674-8115.2024.06.015

受体相互作用蛋白激酶1调节癌症进展和免疫反应的研究现状

张勇¹(), 李伟宏¹, 程志鹏¹, 王斌¹, 王思珩¹, 王毓斌¹^,²()

^1.山西医科大学第五临床医学院，太原 030012
^2.山西医科大学附属山西省人民医院泌尿外科，太原 030012

收稿日期:2024-01-09 接受日期:2024-04-12 出版日期:2024-06-28 发布日期:2024-06-28
通讯作者: 王毓斌 E-mail:840595873@qq.com;wangyb1980@163.com
作者简介:张勇（1997—），男，硕士生；电子信箱：840595873@qq.com。
基金资助:
山西省自然科学研究项目(202103021224375);山西省留学人员科技活动择优资助项目(2022047);山西省回国留学人员科研资助项目(2022-204)

Research status of receptor-interacting protein kinase 1 in regulating cancer progression and immune response

ZHANG Yong¹(), LI Weihong¹, CHENG Zhipeng¹, WANG bin¹, WANG Siheng¹, WANG Yubin¹^,²()

^1.The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030012, China
^2.Department of Urology, Shanxi Provincial People′s Hospital, Shanxi Medical University, Taiyuan 030012, China

Received:2024-01-09 Accepted:2024-04-12 Online:2024-06-28 Published:2024-06-28
Contact: WANG Yubin E-mail:840595873@qq.com;wangyb1980@163.com
Supported by:
Natural Science Foundation of Shanxi Province(202103021224375);Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province(2022047);Research Project Supported by Shanxi Scholarship Council of China(2022-204)

摘要/Abstract

摘要：

受体相互作用蛋白激酶1（receptor-interacting protein kinase 1，RIPK1）是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质，引起下游的信号转导和生物效应。近年来，随着对RIPK1的深入研究，学者发现其在自身免疫性疾病、神经退行性疾病，以及多种实体瘤和血液肿瘤中具有重要意义。一方面，RIPK1通过激活特定通路如核因子-κB（nuclear factor-κB，NF-κB）和丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）等促进细胞存活及炎症反应。另一方面，RIPK1通过与胱天蛋白酶-8（cysteinyl aspartate specific proteinase-8，caspase-8）作用促进凋亡，或与RIPK3和混合谱系激酶结构域样假激酶（mixed lineage kinase domain-like protein，MLKL）作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展，也可以启动机体适应性免疫，抑制肿瘤进展；此外，还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现，可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手，深入探讨其功能，特别是其在调节癌症进展和免疫反应方面的功能，为癌症靶向药物的开发提供新的思路。

关键词: 受体相互作用蛋白激酶1, 坏死性凋亡, 坏死复合物, 癌症, 免疫反应, 靶向治疗

Abstract:

Receptor-interacting protein kinase 1 (RIPK1) is a multi-domain serine/threonine protein kinase that causes downstream signal transduction and biological effects by phosphorylating specific proteins. In recent years, with the in-depth study of RIPK1, scholars have found that it is of great significance in autoimmune diseases, neurodegenerative diseases, and a variety of solid tumors and hematological tumors. On the one hand, RIPK1 promotes cell survival and inflammatory responses by activating specific pathways such as nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). On the other hand, RIPK1 promotes apoptosis by interacting with cysteinyl aspartate specific proteinase-8 (caspase-8), or promotes necroptosis by interacting with RIPK3 and mixed lineage kinase domain-like protein (MLKL). As an upstream signal, RIPK1 has different expression levels in patients with different tumors. Its scaffold function and kinase activity can regulate cancer progression, initiate adaptive immunity, inhibit tumor progression, and generate an immunosuppressive tumor microenvironment to promote tumor development. Its dual role has been demonstrated in regulating the occurrence and development of tumors and the body's immune response, and can be used as a new therapeutic target to control cancer progression. This paper starts with the structure of RIPK1 to further explore its function in regulating cancer progression and immune response, and to provide new ideas for the development of cancer-targeted drugs.

Key words: receptor-interacting protein kinase 1 (RIPK1), necrotizing apoptosis, necrotic complex, cancer, immune response, targeted therapy

中图分类号:

R730.2

张勇, 李伟宏, 程志鹏, 王斌, 王思珩, 王毓斌. 受体相互作用蛋白激酶1调节癌症进展和免疫反应的研究现状[J]. 上海交通大学学报（医学版）, 2024, 44(6): 788-794.

ZHANG Yong, LI Weihong, CHENG Zhipeng, WANG bin, WANG Siheng, WANG Yubin. Research status of receptor-interacting protein kinase 1 in regulating cancer progression and immune response[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(6): 788-794.

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受体相互作用蛋白激酶1调节癌症进展和免疫反应的研究现状

Research status of receptor-interacting protein kinase 1 in regulating cancer progression and immune response

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