Elemento faltante

Este es un articulo importante. Las IAPs (en particular XIAP) son las inhibidoras naturales de las caspasas efectoras y la caspasa 9, de la via intrinseca. Sin embargo no existian las contrapartes de las caspasas de la via extrinseca. Algunos pensaban que la modulacion era mediada solo por FLIP, una proteina parecida a c. 8 sin actividad proteolitica. Sin embargo, El-Deiry identifico a las CARP 1 y 2 como las equivalentes a las IAPs en la via extrinseca. Las CARP habian sido identificadas antes como RHF1, un gen que estaba sobreexpresado en cancer de esofago, pero para el que no tenian funcion (esto no viene en el articulo). Ya tenemos primers de CARP1, que funcionan bien.
Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6170-5
The destruction of cellular targets during apoptosis is carried out by caspases, which are negatively regulated by the inhibitor of apoptosis proteins (IAP); however, death effector domain (DED) caspases of the extrinsic pathway are refractory to the IAP family. We have isolated a family of apoptotic inhibitors [caspases-8- and -10-associated RING proteins (CARPs)] that bind to and negatively regulate DED caspases. When overexpressed, CARPs, via an IAP-like RING domain, can contribute to the ubiquitin-mediated proteolysis of DED caspases. Furthermore, CARPs are rapidly cleaved during apoptosis. However, in tumors and tumor cell lines, they are overexpressed, and their silencing leads to restoration of efficient apoptosis via enhanced activation of DED caspases. Long-term inhibition of CARP expression results in suppression of cancer cell growth, highlighting their importance in tumor cell survival.
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