Association of the HPV-16 E7 oncoprotein with the cullin 2 ubiquitin ligase complex.

摘要: Proc Amer Assoc Cancer Res, Volume 47, 2006 5644 Human papillomaviruses (HPVs) are small DNA viruses that exhibit a tropism for epithelial cells. More than 99% of cervical carcinomas associated with high-risk HPVs. The HPV E6 and E7 proteins consistently expressed in HPV-associated cancers continued expression these viral oncoproteins is necessary the maintenance transformed phenotype. High-risk exhibits diverse oncogenic activities including deregulation cell cycle apoptosis, induction genomic instability degradation retinoblastoma tumor suppressor protein pRB related p107 p130 via ubiquitin proteasome pathway. Alterations steady state levels other cellular E7-expressing cells has also previously been observed. molecular mechanisms how HPV-16 oncoprotein deregulates ubiquitin-proteasome pathway thereby altering targeted not understood. We used tandem affinity purification mass spectrometry to identify complexes. Our results indicate associates cullin 2 ligase complex. complex cosediments E7/pRB,E7/p107 upon glycerol gradient centrifugation. Cullin part Downregulation by RNAi increases positive carcinoma line CaSki. immortalized oral keratinocytes expressing protein. BC box contain conserved motif called (A,P,S,T)LXXXCXXX(A,I,L,V) binding elongin C act as substrate specificity adaptor bring specific degradation. contains two motifs at its C-terminus. binds vitro. Substitutions or deletions some amino acids lead inefficient association vivo. Hence appears determining specificity. data suggest interacting may be recruited aberrant