| First Author | Luo S | Year | 2009 |
| Journal | J Cell Sci | Volume | 122 |
| Issue | Pt 6 | Pages | 875-85 |
| PubMed ID | 19240112 | Mgi Jnum | J:145963 |
| Mgi Id | MGI:3836371 | Doi | 10.1242/jcs.050013 |
| Citation | Luo S, et al. (2009) Huntingtin promotes cell survival by preventing Pak2 cleavage. J Cell Sci 122(Pt 6):875-85 |
| abstractText | Huntington's disease is caused by a polyglutamine expansion in the huntingtin protein. Wild-type huntingtin, by contrast, appears to protect cells from pro-apoptotic insults. Here we describe a novel anti-apoptotic function for huntingtin. When cells are exposed to Fas-related signals, the ubiquitously expressed p21-activated kinase 2 (Pak2) can be activated via cleavage by caspases to release a constitutively active C-terminal fragment, which mediates cell death. Our data show that huntingtin interacts with Pak2. Overexpression of huntingtin significantly inhibits caspase-3-mediated and caspase-8-mediated cleavage of Pak2 in cells. Moreover, huntingtin prevents Pak2 cleavage by caspase-3 and caspase-8 in vitro. Although huntingtin is cytoprotective in wild-type cells that are exposed to TNFalpha, it has no significant benefit in TNFalpha-treated cells with Pak2 knockdown. Thus, huntingtin exerts anti-apoptotic effects by binding to Pak2, which reduces the abilities of caspase-3 and caspase-8 to cleave Pak2 and convert it into a mediator of cell death. |
