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Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53

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1993

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Huibregtse, Jon M.
Howley, Peter M.

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Molecular and Cellular Biology. 1993, 13(2), pp. 775-784. ISSN 0270-7306. eISSN 1098-5549. Available under: doi: 10.1128/MCB.13.2.775

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The E6 oncoproteins of the cancer-associated or high-risk human papillomaviruses (HPVs) target the cellular p53 protein. The association of E6 with p53 leads to the specific ubiquitination and degradation of p53 in vitro, suggesting a model by which E6 deregulates cell growth control by the elimination of the p53 tumor suppressor protein. Complex formation between E6 and p53 requires an additional cellular factor, designated E6-AP (E6-associated protein), which has a native and subunit molecular mass of approximately 100 kDa. Here we report the purification of E6-AP and the cloning of its corresponding cDNA, which contains a novel open reading frame encoding 865 amino acids. E6-AP, translated in vitro, has the following properties: (i) it associates with wild-type p53 in the presence of the HPV16 E6 protein and simultaneously stimulates the association of E6 with p53, (ii) it associates with the high-risk HPV16 and HPV18 E6 proteins in the absence of p53, and (iii) it induces the E6- and ubiquitin-dependent degradation of p53 in vitro.

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570 Biowissenschaften, Biologie

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ISO 690HUIBREGTSE, Jon M., Martin SCHEFFNER, Peter M. HOWLEY, 1993. Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. In: Molecular and Cellular Biology. 1993, 13(2), pp. 775-784. ISSN 0270-7306. eISSN 1098-5549. Available under: doi: 10.1128/MCB.13.2.775
BibTex
@article{Huibregtse1993Cloni-42702,
  year={1993},
  doi={10.1128/MCB.13.2.775},
  title={Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53},
  number={2},
  volume={13},
  issn={0270-7306},
  journal={Molecular and Cellular Biology},
  pages={775--784},
  author={Huibregtse, Jon M. and Scheffner, Martin and Howley, Peter M.}
}
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