title: Physical and functional interaction of the HECT ubiquitin-protein ligases E6AP and HERC2.
abstract: Deregulation of the ubiquitin-protein ligase E6AP contributes to the development of the Angelman syndrome and to cervical carcinogenesis suggesting that the activity of E6AP needs to be under tight control. However, how E6AP activity is regulated at the post-translational level under non-pathologic conditions is poorly understood. In this study, we report that the giant protein HERC2, which is like E6AP a member of the HECT family of ubiquitin-protein ligases, binds to E6AP. The interaction is mediated by the RCC1-like domain 2 of HERC2 and a region spanning amino acid residues 150-200 of E6AP. Furthermore, we provide evidence that HERC2 stimulates the ubiquitin-protein ligase activity of E6AP in vitro and within cells and that this stimulatory effect does not depend on the ubiquitin-protein ligase activity of HERC2. Thus, the data obtained indicate that HERC2 acts as a regulator of E6AP.
authors.affiliation: Department of Biology and Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Kühnle
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kogel
authors.forename: Sandra
authors.initials: S
authors.lastname: Glockzin
authors.forename: Andreas
authors.initials: A
authors.lastname: Marquardt
authors.forename: Aaron
authors.initials: A
authors.lastname: Ciechanover
authors.forename: Konstantin
authors.initials: K
authors.lastname: Matentzoglu
authors.forename: Martin
authors.initials: M
authors.lastname: Scheffner
mesh_terms: D017204:Angelman Syndrome / Q000201:enzymology; D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C486527:Herc2 protein, mouse; C471639:UBE3A protein, human; C118566:HERC2 protein, human; D044767:Ubiquitin-Protein Ligases