Referencia

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

Autores

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.

Resumen

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.

Descripción

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.

Descárgate este artículo aquí.

¿Acabas de publicar un artículo interesante?

Manda la referencia a través de nuestro formulario.  Límite de edad 32 años. Los artículos seleccionados serán destacados como artículos del mes y participarán en el Premio Fisher Scientific, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes

01-04-2017

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...

Leer más

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c

01-03-2017

Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone...

Leer más

The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes

01-02-2017

The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty...

Leer más

Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes

01-01-2017

Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes do not, a distinctive feature that is essential for neurotransmission and neuronal survival. However, any link between these metabolic differences...

Leer más

A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection

01-12-2016

There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways;...

Leer más

In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development

01-11-2016

Class IIa Histone Deacetylases (HDACs) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows...

Leer más

DNA demethylation of inflammasome-associated genes is enhanced in patients with cryopyrin-associated periodic syndromes

01-10-2016

Inflammasomes are cytosolic multiprotein complexes in macrophages. They assemble after infection- or stress-associated stimuli, activating both caspase-1-mediated inflammatory cytokine secretion and pyroptosis. Increased inflammasome activity resulting from gene mutations is...

Leer más

Cysteine Mutational Studies Provide Insight into a Thiol-Based Redox Switch Mechanism of Metal and DNA Binding in FurA from Anabaena sp. PCC 7120

01-09-2016

Aims: The ferric uptake regulator (Fur) is the main transcriptional regulator of genes involved in iron homeostasis in most prokaryotes. FurA from Anabaena sp. PCC 7120 contains five cysteine residues...

Leer más

IL-4 orchestrates STAT6-mediated DNA demethylation leading to dendritic cell differentiation

01-08-2016

The role of cytokines in establishing specific transcriptional programmes in innate immune cells has long been recognized. However, little is known about how these extracellular factors instruct innate immune cell...

Leer más

Dissecting the role of Epidermal Growth Factor Receptor catalytic activity during liver regeneration and hepatocarcinogenesis

01-07-2016

Different data support a role for the epidermal growth factor receptor (EGFR) pathway during liver regeneration and hepatocarcinogenesis. However, important issues, such as the precise mechanisms mediating its actions and...

Leer más

Socios Protectores