| Gene Name | APOBEC3B |
| HF Protein Name | DNA dC->dU-editing enzyme APOBEC-3B |
| HF Function | Restriction factor and involves in virus-associated carcinogenesis |
| Uniprot ID | Q9UH17 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 9582 |
| Host Factor (HF) Name in Paper | APOBEC3B |
| Gene synonyms | N.A. |
| Ensemble Gene ID | ENSG00000179750 |
| Ensemble Transcript | ENST00000333467 [Q9UH17-1];ENST00000335760 [Q9UH17-2];ENST00000407298 [Q9UH17-3] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0003723, GO:0005634, GO:0008270, GO:0010529, GO:0045087, GO:0047844, GO:0051607, |
| MINT ID | N.A. |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 607110 |
| PANTHER ID | N.A. |
| PDB ID(s) | 2NBQ, 5CQD, 5CQH, 5CQI, 5CQK, 5SXG, 5SXH, 5TD5, 5TKM, |
| pfam ID | PF08210, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| Organism | Homo sapiens (Human) |
| Virus Name | Human papillomavirus type 16 |
| Virus Short Name | HPV16 |
| Order | Unassigned |
| Virus Family | Papillomaviridae |
| Virus Subfamily | N.A. |
| Genus | Alphapapillomavirus |
| Species | Human papillomavirus 16 |
| Host | Human, monkeys |
| Cell Tropism | Epithelial cells of skin, mucous membranes |
| Associated Disease | Malignant tumours |
| Mode of Transmission | Sexual, indirect and direct contact, auto-inoculation |
| VIPR DB link | N.A. |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/121/papillomaviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Papillomaviridae |
| Paper Title | Human Papillomavirus 16 E6 Upregulates APOBEC3B via the TEAD Transcription Factor |
| Author's Name | Seiichiro Mori, Takamasa Takeuchi, Yoshiyuki Ishii, Takashi Yugawa, Tohru Kiyono, Hiroshi Nishina, Iwao Kukimoto |
| Journal Name | Journal Of Virology |
| Pubmed ID | 28077648 |
| Abstract | The cytidine deaminase APOBEC3B (A3B) underlies the genetic heterogeneity of several human cancers, including cervical cancer, which is caused by human papillomavirus (HPV) infection. We previously identified a region within the A3B promoter that is activated by the viral protein HPV16 E6 in human keratinocytes. Here, we discovered three sites recognized by the TEAD family of transcription factors within this region of the A3B promoter. Reporter assays in HEK293 cells showed that exogenously expressed TEAD4 induced A3B promoter activation through binding to these sites. Normal immortalized human keratinocytes expressing E6 (NIKS-E6) displayed increased levels of TEAD1/4 protein compared to parental NIKS. A series of E6 mutants revealed that E6-mediated degradation of p53 was important for increasing TEAD4 levels. Knockdown of TEADs in NIKS-E6 significantly reduced A3B mRNA levels, whereas ectopic expression of TEAD4 in NIKS increased A3B mRNA levels. Finally, chromatin immunoprecipitation assays demonstrated increased levels of TEAD4 binding to the A3B promoter in NIKS-E6 compared to NIKS. Collectively, these results indicate that E6 induces upregulation of A3B through increased levels of TEADs, highlighting the importance of the TEAD-A3B axis in carcinogenesis.IMPORTANCEÂ The expression of APOBEC3B (A3B), a cellular DNA cytidine deaminase, is upregulated in various human cancers and leaves characteristic, signature mutations in cancer genomes, suggesting that it plays a prominent role in carcinogenesis. Viral oncoproteins encoded by human papillomavirus (HPV) and polyomavirus have been reported to induce A3B expression, implying the involvement of A3B upregulation in virus-associated carcinogenesis. However, the molecular mechanisms causing A3B upregulation remain unclear. Here, we demonstrate that exogenous expression of the cellular transcription factor TEAD activates the A3B promoter. Further, the HPV oncoprotein E6 increases the levels of endogenous TEAD1/4 protein, thereby leading to A3B upregulation. Since increased levels of TEAD4 are frequently observed in many cancers, an understanding of the direct link between TEAD and A3B upregulation is of broad oncological interest. |
| Used Model | HEK293 cells |
| DOI | 10.1128/JVI.02413-16 |
