| Autor: |
Jia Wen, Han Yao, Zhijie Cao, Donglai Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Fundamental Research, Vol 3, Iss 4, Pp 647-654 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2667-3258 |
| DOI: |
10.1016/j.fmre.2022.03.012 |
| Popis: |
Since the recent discovery of cancer cell-intrinsic programmed cell death protein-1 (PD-1), the mechanisms that manipulate PD-1 functions in tumor development beyond its immune checkpoint roles have become attractive research topics in oncology. Our previous study validated that PD-1 exists in lung cancer cells and is directly transactivated by p53 in a DNA-binding domain (DBD) acetylation-dependent manner. Here, we report that the carboxyl-terminal domain (CTD) of p53 likewise participates in PD-1 transcriptional regulation in cancer cells under different regulatory mechanisms. By mutating the lysine residues within the CTD to mimic either acetylation-deficient or fully acetylated status, we proved that acetylated CTD dramatically impeded p53-mediated transactivation of PD-1. Furthermore, we identified bromodomain-containing protein 4 (BRD4) as a transcriptional coactivator of p53 that facilitates p53-mediated PD-1 transcription. Mechanistically, BRD4 specifically bound to the unacetylated CTD of p53, while CTD acetylation almost completely destroyed the BRD4-p53 interaction and thus led to compromised PD-1 expression. Collectively, this study unveils an alternative mechanism of p53 acetylation-directed PD-1 transcriptional regulation, which would broaden our current understanding of the molecular regulatory network of cancer cell-intrinsic PD-1. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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