TARGETID

T53811

FORMERID

TTDI02206

UNIPROID

VE6_HPV16

TARGNAME

Human papillomavirus protein E6 (HPV E6)

GENENAME

HPV E6

TARGTYPE

Clinical trial target

SYNONYMS

Protein E6; E6

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 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/E6P targets several other substrates to degradation via the proteasome including host NFX1- 91, 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 Bak, 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.

PDBSTRUC

6HKS; 4XR8; 4JOP; 4GIZ; 2LJZ

BIOCLASS

Papillomaviridae E protein

SEQUENCE

MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQLLRREVYDFAFRDLCIVYRDGNPYAVCDKCLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCDLLIRCINCQKPLCPEEKQRHLDKKQRFHNIRGRWTGRCMSCCRSSRTRRETQL

DRUGINFO

VGX-3100

DRUGINFO

Tipapkinogene sovacivec

INTEPATH

telomerasepathway:Regulation of Telomerase