Physical and functional interaction of the HECT ubiquitin-protein ligases E6AP and HERC2.

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.

Involvement of the DNA repair protein hHR23 in p53 degradation.

The stability of the tumor suppressor protein p53 is regulated via the ubiquitin-proteasome-dependent proteolytic pathway. Like most substrates of this pathway, p53 is modified by the attachment of polyubiquitin chains prior to proteasome-mediated degradation. However, the mechanism(s) involved in the delivery of polyubiquitylated p53 molecules to the proteasome are currently unclear.