Elucidating the Role of Prohibitin-1 and Erlins in Lipid Metabolism and Cancer Progression Following UV Irradiation
Abstract
Ultraviolet (UV) radiation is a major environmental contributor to skin cancer, primarily by inducing DNA damage and disrupting key cell signaling pathways.1 In this study, we investigated the roles of Prohibitin-1 (PHB-1) and Erlins, both members of the SPFH protein family,2 in mediating the cellular response to UV-induced stress. Both PHB-1 and Erlins are associated with lipid rafts, specialized membrane microdomains that organize signaling molecules.3 PHB-1 is involved in regulating apoptosis, maintaining mitochondrial integrity, and cell cycle regulation,4, 5while Erlins play key roles in ER-associated degradation (ERAD), regulating lipid metabolism, and apoptosis.6 Our results showed that while total PHB-1 levels remained unchanged after sUV exposure, nuclear translocation of PHB-1 occurred at different time points post-sUV exposure, indicating its role in the nuclear stress response. This translocation, as well as self-aggregation of PHB-1, was found to be cholesterol-dependent, highlighting the importance of lipid rafts in PHB-1 function. The self aggregation of PHB-1 was observed in both HaCaT and MEF cells, suggesting a common mechanism linked to apoptosis regulation under sUV stress. Initial Proximity Ligation Assay (PLA) results indicated increased interaction between PHB-1 and E2F1 specifically at 1 hour post sUV exposure, potentially playing a role in cell cycle regulation. The role of Erlins in ERAD, lipid metabolism, and apoptosis in response to UV exposure is still being investigated and will be further explored in future experiments. Given the critical role of lipid metabolism and ER stress in the development of cancer, understanding Erlins’ involvement in these processes could provide new insights into how UV-induced cellular stress contributes to skin cancer progression. This study is part of our broader effort to uncover the molecular mechanisms driving sUV-induced skin cancer, with the ultimate goal of identifying potential therapeutic targets.
Status
Graduate
Department
Chemistry & Biochemistry
College
College of Arts and Sciences
Campus
Athens
Faculty Mentor
Dr. Shiyong Wu
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Elucidating the Role of Prohibitin-1 and Erlins in Lipid Metabolism and Cancer Progression Following UV Irradiation
Ultraviolet (UV) radiation is a major environmental contributor to skin cancer, primarily by inducing DNA damage and disrupting key cell signaling pathways.1 In this study, we investigated the roles of Prohibitin-1 (PHB-1) and Erlins, both members of the SPFH protein family,2 in mediating the cellular response to UV-induced stress. Both PHB-1 and Erlins are associated with lipid rafts, specialized membrane microdomains that organize signaling molecules.3 PHB-1 is involved in regulating apoptosis, maintaining mitochondrial integrity, and cell cycle regulation,4, 5while Erlins play key roles in ER-associated degradation (ERAD), regulating lipid metabolism, and apoptosis.6 Our results showed that while total PHB-1 levels remained unchanged after sUV exposure, nuclear translocation of PHB-1 occurred at different time points post-sUV exposure, indicating its role in the nuclear stress response. This translocation, as well as self-aggregation of PHB-1, was found to be cholesterol-dependent, highlighting the importance of lipid rafts in PHB-1 function. The self aggregation of PHB-1 was observed in both HaCaT and MEF cells, suggesting a common mechanism linked to apoptosis regulation under sUV stress. Initial Proximity Ligation Assay (PLA) results indicated increased interaction between PHB-1 and E2F1 specifically at 1 hour post sUV exposure, potentially playing a role in cell cycle regulation. The role of Erlins in ERAD, lipid metabolism, and apoptosis in response to UV exposure is still being investigated and will be further explored in future experiments. Given the critical role of lipid metabolism and ER stress in the development of cancer, understanding Erlins’ involvement in these processes could provide new insights into how UV-induced cellular stress contributes to skin cancer progression. This study is part of our broader effort to uncover the molecular mechanisms driving sUV-induced skin cancer, with the ultimate goal of identifying potential therapeutic targets.