Caspase-6 (Casp6) is a short pro-domain caspase that is activated early in Alzheimer disease, yet, little is known on the mechanism of activation of this caspase. In this study, critical proteolytic processing events required for Casp6 activation in vitro and in vivo were evaluated by site directed mutagenesis of the D23 pro-domain, and D179 and D193 linker processing sites. We found that (1) Casp6 was self-processed and activated in vitro and in vivo, (2) uncleavable Casp6 possessed low activity in vitro but not in vivo, (3) the pro-domain of Casp6 entirely prevented self-processing and activation in vivo but not in vitro, (4) removal of the pro-domain promoted Casp6 activation, (5) cleavage at either D179 or D193 was sufficient to generate activity in vitro and in vivo, and (6) Casp6 activity did not induce cell death in HEK293T cells. We conclude that the Casp6 is activated through proteolytic cleavage, as are the effector Caspase-3 and -7. However, unlike other effector caspases, Casp6 can be entirely self-activated and its activation does not necessarily induce cell death.
Pubmed ID: 19133298 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Service that helps users navigate the research journey, connecting people and information from dissertations to governmental and cultural archives to news, in all its forms. Its role is essential to libraries and other organizations whose missions depend on the delivery of complete, trustworthy information. ProQuest''s massive information pool, built through partnerships with content creators, is navigated through technological innovations that enable users to quickly find just the right information. The ProQuest platform moves beyond navigation to empower researchers to use, create, and share contentaccelerating research productivity. The Summon web-scale discovery service is a boon to academic libraries worldwide. ProQuest expanded into corporate and government markets, with the ProQuest Dialog service and acquiring Congressional Information Services and University Publications of America. It acquired ebrary, expanding ProQuest''s content base to include e-books and adding to the technology expertise resident across the enterprise, which also includes such units as Serials Solutions, RefWorks-COS, and Bowker.
View all literature mentions