Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7OU0X)

• DTT Name: Human papillomavirus-18 E6 region messenger RNA (HPV-18 E6 mRNA)
• Synonyms: HPV-18 protein E6 (mRNA); HPV-18 E6 (mRNA)
• Gene Name: HPV-18 E6 mRNA
• DTT Type: Literature-reported target; [1]
• BioChemical Class: mRNA target
• UniProt ID: VE6_HPV18
• TTD ID: T43303
• Sequence:
  MARFEDPTRRPYKLPDLCTELNTSLQDIEITCVYCKTVLELTEVFEFAFKDLFVVYRDSI
  PHAACHKCIDFYSRIRELRHYSDSVYGDTLEKLTNTGLYNLLIRCLRCQKPLNPAEKLRH
  LNEKRRFHNIAGHYRGQCHSCCNRARQERLQRRRETQV
• Function: 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. Plays a major role in the induction and maintenance of cellular transformation.

Molecular Interaction Atlas (MIA) of This DTT

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 2490	DMYEC3M	Discovery agent	N.A.	Investigative	[1]

References

• [1] US patent application no. 5,457,189, Antisense oligonucleotide inhibition of papillomavirus.