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- Title
The resurrection of RIP kinase 1 as an early cell death checkpoint regulator—a potential target for therapy in the necroptosis era.
- Authors
Ju, Eunjin; Park, Kyeong Ah; Shen, Han-Ming; Hur, Gang Min
- Abstract
Receptor-interacting serine threonine protein kinase 1 (RIPK1) has emerged as a central molecular switch in controlling the balance between cell survival and cell death. The pro-survival role of RIPK1 in maintaining cell survival is achieved via its ability to induce NF-κB-dependent expression of anti-apoptotic genes. However, recent advances have identified the pro-death function of RIPK1: posttranslational modifications of RIPK1 in the tumor necrosis factor receptor 1 (TNFR1)-associated complex-I, in the cytosolic complex-IIb or in necrosomes regulate the cytotoxic potential of RIPK1, forming an early cell death checkpoint. Since the kinase activity of RIPK1 is indispensable in RIPK3- and MLKL-mediated necroptosis induction, while it is dispensable in apoptosis, a better understanding of this early cell death checkpoint via RIPK1 might lead to new insights into the molecular mechanisms controlling both apoptotic and necroptotic modes of cell death and help develop novel therapeutic approaches for cancer. Here, we present an emerging view of the regulatory mechanisms for RIPK1 activity, especially with respect to the early cell death checkpoint. We also discuss the impact of dysregulated RIPK1 activity in pathophysiological settings and highlight its therapeutic potential in treating human diseases. Cell biology: a protein controlling whether cells live or die Improved understanding of the molecular mechanisms that allow a protein to control the balance between cell survival or early death could reveal new approaches to treating conditions including chronic inflammatory disease and cancer. Gang Min Hur and colleagues at Chungnam National University in Daejeon, South Korea, with Han-Ming Shen at the University of Macau in China, review emerging evidence about how the protein called receptor-interacting serine/threonine-protein kinase 1 (RIPK1) influences whether cells move towards death or survival at a key 'checkpoint' in cell development. Cells can undergo a natural process of programmed cell death called apoptosis, die abnormally in a disease process called necroptosis, or survive. RIPK1 appears able to influence which path is chosen depending on which genes it regulates and which proteins it interacts with. Many details are still unclear, and need further investigation.
- Publication
Experimental & Molecular Medicine EMM, 2022, Vol 54, Issue 9, p1401
- ISSN
1226-3613
- Publication type
Article
- DOI
10.1038/s12276-022-00847-4