MLKL, a new actor of UVB-induced apoptosis in human diploid dermal fibroblasts
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Published on: June 7, 2019
Anne-Sophie Gary1,2, Sophie Amouret1,2, Alicia Montoni1,2
1Centre de Recherche du CHU de Québec - Université Laval, Axe Médecine Régénératrice, Hôpital du Saint-Sacrement, Québec, QC, Canada.
Abstract:
Ultraviolet radiation (UVR) is a major environmental mutagen. In skin, UVR can initiate cancer through the induction of mutagenic DNA damage and promote its progression. An important cancer prevention mechanism is the regulated cell death (RCD), which can safely dispose of damaged cells. Apoptosis, a well-known RCD, is known to be activated by UVR, but part of the mechanism and proteins involved in UVR-induced apoptosis are still to be discovered. Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) are two proteins involved in necroptosis, a form of RCD. Here, we have evaluated the implication of RIPK3 and MLKL in UVB-induced cell death in human diploid dermal fibroblasts. Our results show that RIPK3 and MLKL play opposite roles in UVB-induced cell death, in a necroptosis independent pathway. We showed that RIPK3 protects cells from UVB cell death, while MLKL sensitizes cells to UVB-induced apoptosis. Taken together these results are the first to show the implication of RIPK3 and MLKL in survival and apoptosis, respectively, bringing two new actors in UVB-induced cell death pathway.
Insights
Ultraviolet radiation (UVR) triggers cell death pathways. Researchers found Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) protects cells, while mixed lineage kinase domain-like (MLKL) promotes apoptosis after UVR exposure.
Area of Science:
- Molecular biology
- Cell biology
- Dermatology
Background:
- Ultraviolet radiation (UVR) is a significant environmental mutagen.
- UVR-induced DNA damage in skin can lead to cancer initiation and progression.
- Regulated cell death (RCD) mechanisms, like apoptosis, are crucial for eliminating damaged cells.
Purpose of the Study:
- To investigate the roles of RIPK3 and MLKL in UVB-induced cell death.
- To elucidate the involvement of these proteins in UVB-induced apoptosis and survival pathways.
Main Methods:
- Utilized human diploid dermal fibroblasts.
- Examined the function of RIPK3 and MLKL in response to UVB irradiation.
- Analyzed cell death and apoptosis signaling pathways.
Main Results:
- RIPK3 and MLKL exhibit opposing roles in UVB-induced cell death.
- RIPK3 demonstrates a protective effect against UVB-induced cell death.
- MLKL sensitizes cells to UVB-induced apoptosis via a necroptosis-independent pathway.
Conclusions:
- RIPK3 and MLKL are newly identified key players in UVB-induced cell death.
- RIPK3 influences cell survival, while MLKL impacts UVB-induced apoptosis.
- These findings contribute to understanding the molecular mechanisms of UVR-induced skin damage and potential therapeutic targets.
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