E6 associated protein

The discovery of this family of E3 enzymes started from the studies on the targeted degradation of the p53 tumor suppressor protein. Ubiquitinylation and degradation of p53 can be mediated by the papillomavirus E6 oncoprotein (see below) in collaboration with a further protein, E6-AP (E6 associated protein). E6-AP was the first member of a large family of E3 enzymes, the Hect (homologous to E6-AP C-terminus ) domain family. These proteins contain an essential active site Cys residue near the C-terminus and one or several WW domains ( see Chapter 8.2.6). 

Xu, Z., Lazim, R., Sun, T, Mei, Y, and Zhang, D. (2012). Solvent effect on the folding dynamics and structure of e6-associated protein characterized from ab initio protein folding simulations. The Joumai of Chemicai Physics 136,13, p. 135102. 

HPV-16 encodes a set of early gene oncoproteins (E6 and E7) responsible for cellular immortalization. HPV types 16 and 18 E6 and E7 proteins are known to interact strongly with p53 and retinoblastoma (Rb) tumor suppressor gene products, respectively (2). The association of E6 with p53 marks this tumor suppressor for rapid ubiquitin-mediated proteolysis. Reduced levels of p53 prevent the cell from activating cell cycle arrest and/or induction of apoptosis in genetically mutated cells. 

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