Reference

Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):310-315. doi: 10.1073/pnas.1612322114. Epub 2016 Dec 27.portada2

Authors

Andreu-Fernández V, Sancho M, Genovés A, Lucendo E, Todt F, Lauterwasser J, Funk K, Jahreis G, Pérez-Payá E, Mingarro I, Edlich F, Orzáez M.

Abstract

The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by prosurvival Bcl-2 proteins. C-terminal Bax transmembrane domain interactions were implicated recently in Bax pore formation. Here, we show that the isolated transmembrane domains of Bax, Bcl-xL (B-cell lymphoma-extra large), and Bcl-2 can mediate interactions between Bax and prosurvival proteins inside the membrane in the absence of apoptotic stimuli. Bcl-2 protein transmembrane domains specifically homooligomerize and heterooligomerize in bacterial and mitochondrial membranes. Their interactions participate in the regulation of Bcl-2 proteins, thus modulating apoptotic activity. Our results suggest that interactions between the transmembrane domains of Bax and antiapoptotic Bcl-2 proteins represent a previously unappreciated level of apoptosis regulation.

Description

El objetivo de este trabajo ha sido el estudio de los dominios transmembrana (TMD) de las proteínas de la familia Bcl-2, las cuales regulan el proceso apoptótico mediante un balance de interacciones proteína-proteína entre los miembros pro- y antiapoptóticos. Los resultados demostraron que los fragmentos transmembrana de Bax, Bcl-2 y Bcl-xL podían estar implicados no sólo en la localización subcelular de las proteínas de la familia Bcl-2 sino también en la red de interacciones que se establece entre ellas así como en su función reguladora de la apoptosis.

 

 

P 20170320

 

REFERENCIA DEL GRUPO INVESTIGADOR

En el laboratorio de Química de Péptidos y Proteínas así como en el de Proteínas de Membrana de la Universidad de Valencia utilizamos una aproximación basada en la biología química y el estudio de las proteínas de membrana para la caracterización de interacciones proteína-proteína de relevancia en patologías y para el desarrollo de moléculas moduladoras que son posibles candidatos a fármacos en patologías relacionadas con los procesos de supervivencia y muerte celular como el cáncer.

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