Systematic identification of interactions between host cell proteins and E7 oncoproteins from diverse human papillomaviruses

摘要: More than 120 human papillomaviruses (HPVs) have now been identified and associated with a variety of clinical lesions. To understand the molecular differences among these viruses that result in lesions distinct pathologies, we begun MS-based proteomic analysis HPV–host cellular protein interactions created plasmid cell line libraries required for studies. validate our system, characterized host proteins bind to E7 expressed from 17 different HPV types. These studies reveal number interactions, some which are conserved across types others unique single species or genus. Binding UBR4/p600 is all virus types, whereas ENC1 binds specifically E7s HPV18 HPV45, both members genus alpha, 7. We identify specific interaction HPV16 ZER1, substrate specificity factor cullin 2 (CUL2)-RING ubiquitin ligase, show ZER1 binding CUL2. further destabilization retinoblastoma tumor suppressor RB1 E7-expressing cells propose CUL2–ZER1 complex functions target degradation cells. refine current understanding establish platform rapid identification virus–host interactions.