Referencia

Nature Communications (2013) 4:1338 doi: 10.1038/ncomms2334. PMID: 23299888

Autores

Isabel Romero Camarero, Xiaoyu Jiang, Yasodha Natkunam, Xiaoqing Lu, Carolina Vicente Dueñas, Ines González Herrero, Teresa Flores, Juan Luis García, George McNamara, Christian Kunder, Shuchun Zhao, Víctor Segura, Lorena Fontán , Jose A. Martínez Climent, Francisco Javier García Criado, Jason D. Theis, Ahmet Dogan, Elena Campos Sánchez, Michael R. Green, Ash A. Alizadeh, César Cobaleda, Isidro Sánchez García, Izidore S. Lossos.

Resumen

The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.

Descripción

HGAL, de las siglas Human Germinal Center Associated Lymphoma es un gen novedoso que fue descrito por primera vez en el año 2003 y, desde entonces, ha sido relacionado con la supervivencia de pacientes con linfoma B difuso de célula grande y linfoma Hodgkin, pero no se conocía su función biológica. Los resultados publicados en Nature Communications, demuestran, que, la expresión no controlada de HGAL produce una hiperplasia linfoide B. El mecanismo molecular que utiliza HGAL está mediado por la activación de la tirosín-quinasa SyK, que altera la señalización del receptor de los linfocitos B. Estos hallazgos sugieren que los inhibidores de SyK podrían llegar a ser útiles en el tratamiento de esta enfermedad.

imagen julio

REFERENCIA DEL GRUPO INVESTIGADOR

El trabajo publicado ha sido posible gracias a la colaboración de los grupos del Dr. Izidore Lossos, en la Universidad de Miami e Isidro Sánchez García, del Instituto de Biología Molecular y Celular del Cáncer de Salamanca. El Dr. Lossos fue uno de los descubridores de HGAL, y la investigación desarrollada en su laboratorio se centra en los genes y mecanismos de patogénesis de linfomas humanos. El grupo del Dr. Sánchez García trabaja en entender los mecanismos moleculares que gobiernan la génesis y mantenimiento de las células stem cancerígenas para el desarrollo de nuevos tratamientos frente al cáncer.

Para ver el artículo completo, pulse aqui

Más artículos en la revista SEBBM.

¿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 al mejor artículo de jóvenes de la SEBBM, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

A Mammalian Target of Rapamycin-Perilipin 3 (mTORC1-Plin3) Pathway is essential to Activate Lipophagy and Protects Against Hepatosteatosis

24-09-2021

Background and Aims: NAFLD is the most common hepatic pathology in western countries and no treatment is currently available. NAFLD is characterized by the aberrant hepatocellular accumulation of fatty acids...

Leer más

NF-κB/IKK activation by small extracellular vesicles within the SASP

07-09-2021

Cellular senescence plays an important role in different biological and pathological conditions. Senescent cells communicate with their microenvironment through a plethora of soluble factors, metalloproteases and extracellular vesicles (EV). Although...

Leer más

α-Helical peptidic scaffolds to target α-synuclein toxic species with nanomolar affinity

28-07-2021

α-Synuclein aggregation is a key driver of neurodegeneration in Parkinson's disease and related syndromes. Accordingly, obtaining a molecule that targets α-synuclein toxic assemblies with high affinity is a long-pursued objective...

Leer más

Neutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism

30-06-2021

Liver metabolism follows diurnal fluctuations through the modulation of molecular clock genes. Disruption of this molecular clock can result in metabolic disease but its potential regulation by immune cells remains...

Leer más

G6PD overexpression protects from oxidative stress and age-related hearing loss

23-05-2021

Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises...

Leer más

Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis

25-04-2021

Chronic kidney disease (CKD) remains a major epidemiological, clinical, and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) present a persistent inflammatory and profibrotic response. Fatty acid oxidation (FAO)...

Leer más

Astrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development

29-03-2021

Presynaptic spike timing-dependent long-term depression (t-LTD) at hippocampal CA3-CA1 synapses is evident until the 3rd postnatal week in mice, disappearing during the 4th week. At more mature stages, we found...

Leer más

Ceramide chain length–dependent protein sorting into selective endoplasmic reticulum exit sites

22-02-2021

Protein sorting in the secretory pathway is crucial to maintain cellular compartmentalization and homeostasis. In addition to coat-mediated sorting, the role of lipids in driving protein sorting during secretory transport...

Leer más

Antigen retrieval and clearing for whole-organ immunofluorescence by FLASH

25-01-2021

Advances in light-sheet and confocal microscopy now allow imaging of cleared large biological tissue samples and enable the 3D appreciation of cell and protein localization in their native organ environment...

Leer más

Viral Bcl2s' transmembrane domain interact with host Bcl2 proteins to control cellular apoptosis

08-01-2021

Viral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis...

Leer más

Socios Protectores