• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Mind bomb 1 regulation of cFLIP interactions.

Mind bomb 1 (Mib1) is a multidomain E3 ligase that directs ubiquitination of the Notch ligands Delta and Jagged to promote their endocytosis. Here we examine Notch-independent functions of Mib1 and find that its activities are linked to the initiation of the extrinsic cell death pathway. Expression of Mib1 induces a spontaneous, caspase-dependent cell death. Consistent with this, depletion of endogenous Mib1 decreases tumor-necrosis factor (TNF)-induced cell death. Mib1 was found to bind to cellular Fas-associated death domain (FADD)-like IL-1b converting enzyme (FLICE)-like inhibitory proteins (cFLIP-L and cFLIP-S), whereas only cFLIP-s can inhibit Mib1-induced cell death. The interaction between Mib1 and cFLIP decreases the association of caspase-8 with cFLIP, which activates caspase-8 and induces cell death. Collectively, these results suggest that in addition to a central role in Notch signaling, Mib1 has an important role in regulating the extrinsic cell death pathway.

Pubmed ID: 19710364