Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma
Abstract. Background:. The hepatitis B virus X (HBx) protein plays a critical role in the initiation and progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). In the early stage of the disease, HBx facilitates tumor onset by inactivating the tumor suppressor p53. The p53-...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2022-07-01
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| Series: | Chinese Medical Journal |
| Online Access: | http://journals.lww.com/10.1097/CM9.0000000000002283 |
| _version_ | 1811258770705088512 |
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| author | Bangxiang Xie Qian Hao Xiang Zhou Dexi Chen Yuanyuan Ji |
| author_facet | Bangxiang Xie Qian Hao Xiang Zhou Dexi Chen Yuanyuan Ji |
| author_sort | Bangxiang Xie |
| collection | DOAJ |
| description | Abstract. Background:. The hepatitis B virus X (HBx) protein plays a critical role in the initiation and progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). In the early stage of the disease, HBx facilitates tumor onset by inactivating the tumor suppressor p53. The p53-encoding gene, however, is frequently mutated or deleted as the cancer progresses to the late stage and, under such circumstance, the p53 homolog TAp63 can harness HCC growth by transactivating several important p53-target genes.
Methods:. To determine whether HBx regulates TAp63, we performed co-immunoprecipitation assay, real-time quantitative polymerase chain reaction, immunoblotting, and flow cytometry analysis in p53-null cancer cell lines, Hep3B and H1299.
Results:. HBx interacts with the transactivation domain of TAp63, as HBx was co-immunoprecipitated with TAp63 but not with ΔNp63. The interaction between HBx and TAp63 abolished transcriptional activity of TAp63, as evidenced by the reduction of the levels of its target genes p21 and PUMA, consequently leading to restricted apoptosis and augmented proliferation of HCC cells.
Conclusion:. HBV induces progression of HCC that harbors defective p53 by inhibiting the tumor suppressor TAp63. |
| first_indexed | 2024-04-12T18:19:34Z |
| format | Article |
| id | doaj.art-3f6774d080974b11be48fff0c32cca98 |
| institution | Directory Open Access Journal |
| issn | 0366-6999 2542-5641 |
| language | English |
| last_indexed | 2024-04-12T18:19:34Z |
| publishDate | 2022-07-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj.art-3f6774d080974b11be48fff0c32cca982022-12-22T03:21:30ZengWolters KluwerChinese Medical Journal0366-69992542-56412022-07-01135141728173310.1097/CM9.0000000000002283202207200-00012Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinomaBangxiang XieQian HaoXiang ZhouDexi ChenYuanyuan JiAbstract. Background:. The hepatitis B virus X (HBx) protein plays a critical role in the initiation and progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). In the early stage of the disease, HBx facilitates tumor onset by inactivating the tumor suppressor p53. The p53-encoding gene, however, is frequently mutated or deleted as the cancer progresses to the late stage and, under such circumstance, the p53 homolog TAp63 can harness HCC growth by transactivating several important p53-target genes. Methods:. To determine whether HBx regulates TAp63, we performed co-immunoprecipitation assay, real-time quantitative polymerase chain reaction, immunoblotting, and flow cytometry analysis in p53-null cancer cell lines, Hep3B and H1299. Results:. HBx interacts with the transactivation domain of TAp63, as HBx was co-immunoprecipitated with TAp63 but not with ΔNp63. The interaction between HBx and TAp63 abolished transcriptional activity of TAp63, as evidenced by the reduction of the levels of its target genes p21 and PUMA, consequently leading to restricted apoptosis and augmented proliferation of HCC cells. Conclusion:. HBV induces progression of HCC that harbors defective p53 by inhibiting the tumor suppressor TAp63.http://journals.lww.com/10.1097/CM9.0000000000002283 |
| spellingShingle | Bangxiang Xie Qian Hao Xiang Zhou Dexi Chen Yuanyuan Ji Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma Chinese Medical Journal |
| title | Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma |
| title_full | Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma |
| title_fullStr | Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma |
| title_full_unstemmed | Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma |
| title_short | Inactivation of tumor suppressor TAp63 by hepatitis B virus X protein in hepatocellular carcinoma |
| title_sort | inactivation of tumor suppressor tap63 by hepatitis b virus x protein in hepatocellular carcinoma |
| url | http://journals.lww.com/10.1097/CM9.0000000000002283 |
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