| Autor: |
Lin Jin, Mahendra P. Kashyap, Yunjia Chen, Jasim Khan, Yuanyuan Guo, Jari Q. Chen, Madison B. Lee, Zhiping Weng, Allen Oak, Prasanth Patcha, Tiffany Mayo, Rajesh Sinha, Venkatram Atigadda, Shahid M. Mukhtar, Jessy S. Deshane, Chander Raman, Carly Elston, Boni E. Elewski, Craig A. Elmets, Mohammad Athar |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 26, Iss 6, Pp 106896- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2023.106896 |
| Popis: |
Summary: Hidradenitis suppurativa (HS) is a skin disorder that causes chronic painful inflammation and hyperproliferation, often with the comorbidity of invasive keratoacanthoma (KA). Our research, employing high-resolution immunofluorescence and data science approaches together with confirmatory molecular analysis, has identified that the 5′-cap-dependent protein translation regulatory complex eIF4F is a key factor in the development of HS and is responsible for regulating follicular hyperproliferation. Specifically, eIF4F translational targets, Cyclin D1 and c-MYC, orchestrate the development of HS-associated KA. Although eIF4F and p-eIF4E are contiguous throughout HS lesions, Cyclin D1 and c-MYC have unique spatial localization and functions. The keratin-filled crater of KA is formed by nuclear c-MYC-induced differentiation of epithelial cells, whereas the co-localization of c-MYC and Cyclin D1 provides oncogenic transformation by activating RAS, PI3K, and ERK pathways. In sum, we have revealed a novel mechanism underlying HS pathogenesis of follicular hyperproliferation and the development of HS-associated invasive KA. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
