EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer
Abstract Ferroptosis is a form of regulated cell death characterized by oxidative injury-induced lipid peroxidation. However, the detailed protein post-translational modification regulatory mechanism of ferroptosis remains largely unknown. Here, we report that E1A binding protein P300 (EP300) acetyl...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-42136-8 |
| _version_ | 1797452720428285952 |
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| author | Yuan Wang Yang Liu Cong Wang Rui Kang Daolin Tang Jiao Liu |
| author_facet | Yuan Wang Yang Liu Cong Wang Rui Kang Daolin Tang Jiao Liu |
| author_sort | Yuan Wang |
| collection | DOAJ |
| description | Abstract Ferroptosis is a form of regulated cell death characterized by oxidative injury-induced lipid peroxidation. However, the detailed protein post-translational modification regulatory mechanism of ferroptosis remains largely unknown. Here, we report that E1A binding protein P300 (EP300) acetyltransferase promotes ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells via the acetylation of heat shock protein family A (Hsp70) member 5 (HSPA5), also known as GRP78 or BIP) on the site of K353. Acetylated HSPA5 loses its ability to inhibit lipid peroxidation and subsequent ferroptotic cell death. Genetic or pharmacological inhibition of EP300-mediated HSPA5 acetylation on K353 increases PDAC cell resistance to ferroptosis. Moreover, histone deacetylase 6 (HDAC6) limits HSPA5 acetylation and subsequent ferroptosis. Collectively, these findings not only identify regulatory pathways for HSPA5 acetylation during ferroptosis, but also highlight promising strategies to increase ferroptosis sensitivity in PDAC cells. |
| first_indexed | 2024-03-09T15:12:44Z |
| format | Article |
| id | doaj.art-64b097e875a940f488bdaaaa90417409 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:12:44Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-64b097e875a940f488bdaaaa904174092023-11-26T13:16:00ZengNature PortfolioScientific Reports2045-23222023-09-0113111110.1038/s41598-023-42136-8EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancerYuan Wang0Yang Liu1Cong Wang2Rui Kang3Daolin Tang4Jiao Liu5DAMP Laboratory, Third Affiliated Hospital of Guangzhou Medical UniversityDAMP Laboratory, Third Affiliated Hospital of Guangzhou Medical UniversityDAMP Laboratory, Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Surgery, UT Southwestern Medical CenterDepartment of Surgery, UT Southwestern Medical CenterDAMP Laboratory, Third Affiliated Hospital of Guangzhou Medical UniversityAbstract Ferroptosis is a form of regulated cell death characterized by oxidative injury-induced lipid peroxidation. However, the detailed protein post-translational modification regulatory mechanism of ferroptosis remains largely unknown. Here, we report that E1A binding protein P300 (EP300) acetyltransferase promotes ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells via the acetylation of heat shock protein family A (Hsp70) member 5 (HSPA5), also known as GRP78 or BIP) on the site of K353. Acetylated HSPA5 loses its ability to inhibit lipid peroxidation and subsequent ferroptotic cell death. Genetic or pharmacological inhibition of EP300-mediated HSPA5 acetylation on K353 increases PDAC cell resistance to ferroptosis. Moreover, histone deacetylase 6 (HDAC6) limits HSPA5 acetylation and subsequent ferroptosis. Collectively, these findings not only identify regulatory pathways for HSPA5 acetylation during ferroptosis, but also highlight promising strategies to increase ferroptosis sensitivity in PDAC cells.https://doi.org/10.1038/s41598-023-42136-8 |
| spellingShingle | Yuan Wang Yang Liu Cong Wang Rui Kang Daolin Tang Jiao Liu EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer Scientific Reports |
| title | EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer |
| title_full | EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer |
| title_fullStr | EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer |
| title_full_unstemmed | EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer |
| title_short | EP300 promotes ferroptosis via HSPA5 acetylation in pancreatic cancer |
| title_sort | ep300 promotes ferroptosis via hspa5 acetylation in pancreatic cancer |
| url | https://doi.org/10.1038/s41598-023-42136-8 |
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