| First Author | Fombonne J | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 26 | Pages | 10510-5 |
| PubMed ID | 22679284 | Mgi Jnum | J:185599 |
| Mgi Id | MGI:5429467 | Doi | 10.1073/pnas.1200094109 |
| Citation | Fombonne J, et al. (2012) Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9. Proc Natl Acad Sci U S A 109(26):10510-5 |
| abstractText | Patched (Ptc), the main receptor for Sonic Hedghog, is a tumor suppressor. Ptc has been shown to be a dependence receptor, and as such triggers apoptosis in the absence of its ligand. This apoptosis induction occurs through the recruitment by the Ptc intracellular domain of a caspase-activating complex, which includes the adaptor proteins DRAL and TUCAN, and the apical caspase-9. We show here that this caspase-activating complex also includes the E3 ubiquitin ligase NEDD4. We demonstrate that Ptc-mediated apoptosis and Ptc-induced caspase-9 activation require NEDD4. We show that Ptc, but not Bax, the prototypical inducer of the intrinsic cell-death pathway, triggers polyubiquitination of caspase-9. Moreover, a caspase-9 mutant that could not be ubiquitinated failed to mediate Ptc-induced apoptosis. Taken together, these data support the view that the Ptc dependence receptor specifically allows the activation of caspase-9 via its ubiquitination, which occurs via the recruitment by Ptc of NEDD4. |
