Axotrophin a RING-variant domain protein acts as E3-ubiquitin-ligase and ubiquitinates the microtubule-associated protein tau

Axotrophin harbours a C4HC3 zinc-finger-like motif in the C-terminus, which is referred to as Ring-variant domain and has been implicated in protein ubiquitination. Recombinant expression and refolding of the C-terminus of axotrophin allowed us to test the E3-ubiquitinligase activity. We found that axotrophin shows E3-ubiquitin-ligase activity in combination with several E2 enzymes and becomes autoubiquitinated. Ubiquitination of tau protein but not KLC1, another axotrophin-interacting protein, was mediated by axotrophin. Further investigation of ubiquitination effects on the protein tau will give more insights about the E3-ubiquitinligase axotrophin and especially its role in AD. from Annual Meeting of the Study Group Neurochemistry. International Conference of the Gesellschaft fur Biochemie und Molekularbiologie 2006 (GBM 2006): Molecular pathways in health and disease of the nervous system Witten, Germany. 28–30 September 2006