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Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2012

Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9.

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Abstract

Patched (Ptc), the main receptor for Sonic Hedgehog, 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.
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Dates and versions

inserm-00721053 , version 1 (07-12-2012)

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Joanna Fombonne, Pierre-Antoine Bissey, Catherine Guix, Rémy Sadoul, Chantal Thibert, et al.. Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9.. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109 (26), pp.10510-5. ⟨10.1073/pnas.1200094109⟩. ⟨inserm-00721053⟩
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