HPV18 E6

Human papillomavirus is a DNA virus from the papillomavirus family, of which over 150 types are known. More than 40 types are transmitted through sexual contact and infect the anus and genitals. HPV is typically spread by sustained direct skin-to-skin contact with vaginal and anal sex being the most common methods.

HPV18 E6

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.

Modulation by virus of host apoptotic process Source: UniProtKB-KW
Modulation by virus of host ubiquitin-protein ligase activity Source: UniProtKB-UniRule
Negative regulation of transcription, DNA-templated Source: CACAO
Suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-UniRule
Suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity Source: UniProtKB-UniRule
Transcription, DNA-templated Source: UniProtKB-UniRule

Host cytoplasm; Host nucleus