2D1030 TRIM11, a tripartite motif protein binds and destabilizes Humanin, a neuroprotective peptideagainst Alzheimer's disease-relevant insults

Humanin (HN) has been identified as a novel neuroprptective peptide that antagonizesneurotoxicity by Alzheimer's disease (AD)-relevant insults, including familial AD-linked mutant genes and amyloid & beta. Expression of HN was observed in the human AD brain aswell as in mouse testis and colon by immunoblot and immunohistochemical analysis. However, little has been known about the regulation of FIN production. By means of yeast two-hybridscreening, we identified TRIM 11 as a novel HN-interacting protein. TRIM 11, which is a member ofprotein family containing a tripartite motif (TRIM), is composed of a RING finger, B-box, coiled-coil, and B30.2 domains. For the interaction of TRIM 11 with HN, the B30. 2 domain wasnecessary together with the coiled-coil domain. The intracellular level of HN peptides wasdrastically reduced by the co-expression of TRIM11. Disruption of the RING finger domain, whichis a putative E3 ubiquitin ligase, or proteasome inhibitor treatment significantly diminishedthe effect of TRIM11 on the intracellular level of HN. These results suggest that TRIM11 plays arole in the regulation of intracellular HN level through ubiquitin-mediated protein degradation.