2006
DOI: 10.1016/j.molcel.2006.01.024
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Structural and Functional Analysis of E6 Oncoprotein: Insights in the Molecular Pathways of Human Papillomavirus-Mediated Pathogenesis

Abstract: Oncoprotein E6 is essential for oncogenesis induced by human papillomaviruses (HPVs). The solution structure of HPV16-E6 C-terminal domain reveals a zinc binding fold. A model of full-length E6 is proposed and analyzed in the context of HPV evolution. E6 appears as a chameleon protein combining a conserved structural scaffold with highly variable surfaces participating in generic or specialized HPV functions. We investigated surface residues involved in two specialized activities of high-risk genital HPV E6: p… Show more

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Cited by 164 publications
(228 citation statements)
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“…However, our analysis of K14E6 WT transgenic mice expressing either a defective E6AP ubiquitin ligase or no E6AP at all demonstrates that E6 retains its ability to abrogate the DNA damage responses and prevents accumulation of mouse p53 in the epidermis. Our result showing that the ubiquitin ligase activity of E6AP is dispensable for E6's inactivation of mouse p53 is consistent with a recent report by Nomine et al (2006) investigating E6's inactivation of human p53, but differs in that we provide evidence that the protein E6AP itself is also not required to degrade mouse p53. Perhaps the difference in the dependence on E6AP for E6-mediated degradation of p53 reflects the species type of p53 being investigated.…”
Section: E6ap Is Not Required For E6's Inactivation Of Mouse P53supporting
confidence: 92%
See 1 more Smart Citation
“…However, our analysis of K14E6 WT transgenic mice expressing either a defective E6AP ubiquitin ligase or no E6AP at all demonstrates that E6 retains its ability to abrogate the DNA damage responses and prevents accumulation of mouse p53 in the epidermis. Our result showing that the ubiquitin ligase activity of E6AP is dispensable for E6's inactivation of mouse p53 is consistent with a recent report by Nomine et al (2006) investigating E6's inactivation of human p53, but differs in that we provide evidence that the protein E6AP itself is also not required to degrade mouse p53. Perhaps the difference in the dependence on E6AP for E6-mediated degradation of p53 reflects the species type of p53 being investigated.…”
Section: E6ap Is Not Required For E6's Inactivation Of Mouse P53supporting
confidence: 92%
“…E6's inactivation of human p53 has been argued to be E6AP dependent based upon the use of antisense oligomers (Traidej et al, 2000), a dominant-negative E6AP (Talis et al, 1998) and small interfering RNAs (siRNAs) (Hengstermann et al, 2001(Hengstermann et al, , 2005Kelley et al, 2005). In particular, siRNA-mediated knockdown of E6AP in HPV16-positive cervical cancer-derived cell lines resulted in the same upregulation of p53-responsive genes as seen with E6 siRNAs (Kelley et al, 2005;Nomine et al, 2006). Thus, we originally hypothesized that E6's inactivation and degradation of mouse p53 would also be E6AP dependent, as in the case for human p53.…”
Section: E6ap Is Not Required For E6's Inactivation Of Mouse P53mentioning
confidence: 99%
“…For SAP97 PDZ2, a peptide corresponding to the disordered C-terminus of the E6 protein was used. 39 The peptide for PTP-BL PDZ2 was derived from the guanine nucleotide exchange factor RA-GEF-2. [36][37][38] The binding between peptides and PDZ domains involves backbone as well as side chain interactions.…”
Section: Resultsmentioning
confidence: 99%
“…HPV16 E6 protein is a multifunctional protein of 19 kDa composed of two zinc-binding domains (Lipari et al, 2001;Nomine´et al, 2003Nomine´et al, , 2006. E6 elicits the polyubiquitination of p53 and its degradation by the 26S proteasome (Scheffner et al, 1990).…”
Section: Introductionmentioning
confidence: 99%
“…We recently identified a p53 degradation-defective mutant of HPV16 E6 (E6 F47R 6C6S), which restored p53 protein in HeLa cells (Nomine´et al, 2006). In our earlier study, we had introduced the F47R mutation in the context of a biochemically stabilized 16E6 mutant, namely E6 6C6S.…”
Section: Introductionmentioning
confidence: 99%