Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell Lines
HBx, a multifunctional regulatory protein, plays an essential role in the replication and pathogenesis of the hepatitis B virus (HBV). In this study, we found that in human hepatoma cells, the tumor suppressor p53 downregulates HBx via ubiquitin-dependent proteasomal degradation. p53 transcriptional...
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MDPI AG
2022-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/10/2313 |
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| author | Ha-Yeon Lim Jiwoo Han Hyunyoung Yoon Kyung Lib Jang |
| author_facet | Ha-Yeon Lim Jiwoo Han Hyunyoung Yoon Kyung Lib Jang |
| author_sort | Ha-Yeon Lim |
| collection | DOAJ |
| description | HBx, a multifunctional regulatory protein, plays an essential role in the replication and pathogenesis of the hepatitis B virus (HBV). In this study, we found that in human hepatoma cells, the tumor suppressor p53 downregulates HBx via ubiquitin-dependent proteasomal degradation. p53 transcriptional activity that results from HBV infection was not essential for this effect. This was shown by treatment with a potent p53 inhibitor, pifithrin-α. Instead, we found that p53 facilitated the binding of E6-associated protein (E6AP), which is an E3 ligase, to HBx and induced E6AP-mediated HBx ubiquitination in a ternary complex of p53, E6AP, and HBx. The ability of p53 to induce E6AP-mediated downregulation of HBx and inhibit HBV replication was demonstrated in an in vitro HBV infection system. This study may provide insights into the regulation of HBx and HBV replication, especially with respect to p53 status, which may also help in understanding HBV-associated tumorigenesis in patients. |
| first_indexed | 2024-03-09T19:23:25Z |
| format | Article |
| id | doaj.art-e9fc7faaf5304f2492ef99c21b2df9e4 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T19:23:25Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e9fc7faaf5304f2492ef99c21b2df9e42023-11-24T03:11:17ZengMDPI AGViruses1999-49152022-10-011410231310.3390/v14102313Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell LinesHa-Yeon Lim0Jiwoo Han1Hyunyoung Yoon2Kyung Lib Jang3Department of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, KoreaDepartment of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, KoreaDepartment of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, KoreaDepartment of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, KoreaHBx, a multifunctional regulatory protein, plays an essential role in the replication and pathogenesis of the hepatitis B virus (HBV). In this study, we found that in human hepatoma cells, the tumor suppressor p53 downregulates HBx via ubiquitin-dependent proteasomal degradation. p53 transcriptional activity that results from HBV infection was not essential for this effect. This was shown by treatment with a potent p53 inhibitor, pifithrin-α. Instead, we found that p53 facilitated the binding of E6-associated protein (E6AP), which is an E3 ligase, to HBx and induced E6AP-mediated HBx ubiquitination in a ternary complex of p53, E6AP, and HBx. The ability of p53 to induce E6AP-mediated downregulation of HBx and inhibit HBV replication was demonstrated in an in vitro HBV infection system. This study may provide insights into the regulation of HBx and HBV replication, especially with respect to p53 status, which may also help in understanding HBV-associated tumorigenesis in patients.https://www.mdpi.com/1999-4915/14/10/2313E6-associated proteinhepatitis B virusproteasomeHBxp53 |
| spellingShingle | Ha-Yeon Lim Jiwoo Han Hyunyoung Yoon Kyung Lib Jang Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell Lines Viruses E6-associated protein hepatitis B virus proteasome HBx p53 |
| title | Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell Lines |
| title_full | Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell Lines |
| title_fullStr | Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell Lines |
| title_full_unstemmed | Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell Lines |
| title_short | Tumor Suppressor p53 Inhibits Hepatitis B Virus Replication by Downregulating HBx via E6AP-Mediated Proteasomal Degradation in Human Hepatocellular Carcinoma Cell Lines |
| title_sort | tumor suppressor p53 inhibits hepatitis b virus replication by downregulating hbx via e6ap mediated proteasomal degradation in human hepatocellular carcinoma cell lines |
| topic | E6-associated protein hepatitis B virus proteasome HBx p53 |
| url | https://www.mdpi.com/1999-4915/14/10/2313 |
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