General Information of the m6A Target Gene (ID: M6ATAR00598)
Target Name Protein E6 (E6)
Gene Name E6
Family Papillomaviridae E6 protein family
Function
Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host UBE3A/E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6AP targets several other substrates to degradation via the proteasome including host DLG1 or NFX1, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including BAK1, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.
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Uniprot ID
VE6_HPV16
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
E6 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 3 (METTL3) [WRITER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Overexpression of the ALKBH5 promoted production of intron retention on the human papillomavirus type 16 (HPV16) E6 mRNAs thereby promoting Protein E6 (E6) mRNA production.METLL3 induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of YTHDC1, enhanced retention of the E6-encoding intron and promoted E6 mRNA production. HPV16 mRNAs are m6A-methylated in tonsillar cancer cells.
Target Regulation Up regulation
Responsed Disease Malignant neoplasms of tonsil ICD-11: 2B69
In-vitro Model WSU-HN26 Squamous cell carcinoma of the oral cavity Homo sapiens CVCL_5523
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
C33A2 (The C33A2 cell line originates from C33A and has the subgenomic HPV16 plasmid pBELsLuc stably integrated into the genome)
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Overexpression of the ALKBH5 promoted production of intron retention on the human papillomavirus type 16 (HPV16) Protein E6 (E6) mRNAs thereby promoting E6 mRNA production. METLL3 induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of YTHDC1, enhanced retention of the E6-encoding intron and promoted E6 mRNA production. HPV16 mRNAs are m6A-methylated in tonsillar cancer cells.
Target Regulation Up regulation
Responsed Disease Malignant neoplasms of tonsil ICD-11: 2B69
In-vitro Model WSU-HN26 Squamous cell carcinoma of the oral cavity Homo sapiens CVCL_5523
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
C33A2 (The C33A2 cell line originates from C33A and has the subgenomic HPV16 plasmid pBELsLuc stably integrated into the genome)
YTH domain-containing protein 1 (YTHDC1) [READER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Overexpression of the ALKBH5 promoted production of intron retention on the human papillomavirus type 16 (HPV16) E6 mRNAs thereby promoting Protein E6 (E6) mRNA production. METLL3 induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of YTHDC1, enhanced retention of the E6-encoding intron and promoted E6 mRNA production. HPV16 mRNAs are m6A-methylated in tonsillar cancer cells.
Target Regulation Up regulation
Responsed Disease Malignant neoplasms of tonsil ICD-11: 2B69
In-vitro Model WSU-HN26 Squamous cell carcinoma of the oral cavity Homo sapiens CVCL_5523
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
C33A2 (The C33A2 cell line originates from C33A and has the subgenomic HPV16 plasmid pBELsLuc stably integrated into the genome)
Malignant neoplasms of tonsil [ICD-11: 2B69]
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Overexpression of the ALKBH5 promoted production of intron retention on the human papillomavirus type 16 (HPV16) E6 mRNAs thereby promoting Protein E6 (E6) mRNA production.METLL3 induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of YTHDC1, enhanced retention of the E6-encoding intron and promoted E6 mRNA production. HPV16 mRNAs are m6A-methylated in tonsillar cancer cells.
Responsed Disease Malignant neoplasms of tonsil [ICD-11: 2B69]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
In-vitro Model WSU-HN26 Squamous cell carcinoma of the oral cavity Homo sapiens CVCL_5523
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
C33A2 (The C33A2 cell line originates from C33A and has the subgenomic HPV16 plasmid pBELsLuc stably integrated into the genome)
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary Overexpression of the ALKBH5 promoted production of intron retention on the human papillomavirus type 16 (HPV16) Protein E6 (E6) mRNAs thereby promoting E6 mRNA production. METLL3 induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of YTHDC1, enhanced retention of the E6-encoding intron and promoted E6 mRNA production. HPV16 mRNAs are m6A-methylated in tonsillar cancer cells.
Responsed Disease Malignant neoplasms of tonsil [ICD-11: 2B69]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
In-vitro Model WSU-HN26 Squamous cell carcinoma of the oral cavity Homo sapiens CVCL_5523
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
C33A2 (The C33A2 cell line originates from C33A and has the subgenomic HPV16 plasmid pBELsLuc stably integrated into the genome)
Experiment 3 Reporting the m6A-centered Disease Response [1]
Response Summary Overexpression of the ALKBH5 promoted production of intron retention on the human papillomavirus type 16 (HPV16) E6 mRNAs thereby promoting Protein E6 (E6) mRNA production. METLL3 induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of YTHDC1, enhanced retention of the E6-encoding intron and promoted E6 mRNA production. HPV16 mRNAs are m6A-methylated in tonsillar cancer cells.
Responsed Disease Malignant neoplasms of tonsil [ICD-11: 2B69]
Target Regulator YTH domain-containing protein 1 (YTHDC1) READER
Target Regulation Up regulation
In-vitro Model WSU-HN26 Squamous cell carcinoma of the oral cavity Homo sapiens CVCL_5523
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
C33A2 (The C33A2 cell line originates from C33A and has the subgenomic HPV16 plasmid pBELsLuc stably integrated into the genome)
References
Ref 1 Overexpression of m6A-factors METTL3, ALKBH5, and YTHDC1 alters HPV16 mRNA splicing. Virus Genes. 2022 Apr;58(2):98-112. doi: 10.1007/s11262-022-01889-6. Epub 2022 Feb 21.