TRIM21-SERPINB5 aids GMPS repression to protect nasopharyngeal carcinoma cells from radiation-induced apoptosis
Posted 16 Apr 2019
bioRxiv DOI: 10.1101/609743 (published DOI: 10.1186/s12929-020-0625-7)
Posted 16 Apr 2019
Nasopharyngeal carcinoma (NPC) is the most prevalent head and neck malignancy in South China and Southeast Asia. The main NPC treatment strategy is radiotherapy. However, recurrence resulting from radioresistance is a leading clinical bottleneck. Revealing the mechanism of NPC radioresistance would help improve the therapeutic effect. Here, our work reveals that TRIM21 (tripartite motif-containing 21) functions as an oncogene in NPC progression, and its ablation increases NPC cell radiosensitivity. Further analysis indicated that TRIM21 represses TP53 expression by mediating GMPS (guanine monophosphate synthase) ubiquitination and degradation after ionizing radiation. Mass spectrometry and co-immunoprecipitation showed that SERPINB5 (serpin family B member 5) interacts with both TRIM21 and GMPS. Epistatic analysis showed that SERPINB5 acts as an adaptor to recruit GMPS and introduce TRIM21 for ubiquitination. The in vitro and in vivo results validated the finding that SERPINB5 promotes NPC cell radioresistance. Furthermore, immunohistochemistry indicated that radioresistant patients have higher SERPINB5 expression. Overall, our data show that TRIM21-SERPINB5-mediated GMPS degradation facilitates TP53 repression, which promotes the radioresistance of NPC cells.
- Downloaded 206 times
- Download rankings, all-time:
- Site-wide: 94,516
- In cancer biology: 2,899
- Year to date:
- Site-wide: 59,663
- Since beginning of last month:
- Site-wide: 65,901
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!