• Inicio
  • Resultados de la búsqueda
  • Human antigen R-mediated mRNA stabilization is required for ultraviolet B-induced autoinduction of amphiregulin in keratinocytes.

Human antigen R-mediated mRNA stabilization is required for ultraviolet B-induced autoinduction of amphiregulin in keratinocytes.

The Journal of biological chemistry (2013-02-23)
Hironao Nakayama, Shinji Fukuda, Natsuki Matsushita, Hisayo Nishida-Fukuda, Hirofumi Inoue, Yuji Shirakata, Koji Hashimoto, Shigeki Higashiyama
RESUMEN

All members of the EGF family are produced as transmembrane precursors that are proteolytically processed into soluble forms by disintegrin and metalloproteinases (ADAMs) for autocrine/paracrine pathways. In turn, the ligand-activated EGF receptor (EGFR) induces the expression of EGF family members, so-called "autoinduction." However, it is not well understood how this autoinduction occurs. In this study, we investigated the molecular mechanism of the autoinduction of amphiregulin (AREG), a member of the EGF family. We found that ultraviolet B (UVB) exposure increased the AREG mRNA level by stabilization of its mRNA in a human immortalized keratinocyte cell line, HaCaT. The 3' UTR of AREG mRNA was responsible for binding to an mRNA-binding protein, human antigen R (HuR), and the interaction between AREG mRNA and HuR was enhanced by UVB. Inducible knockdown of HuR expression significantly decreased AREG mRNA stability. Interestingly, treatment of HaCaT cells with an EGFR inhibitor, an EGFR neutralizing antibody, or an ADAM inhibitor destabilized AREG mRNA. In the case of ADAM inhibition, administration of soluble AREG restored the mRNA level, indicating that the stabilization occurs in a shedding-dependent manner of EGFR ligands. The HuR dependence of AREG mRNA and protein expression was also confirmed in human primary keratinocytes. Taken together, we propose a novel mechanism by which HuR regulates the stability of AREG mRNA in keratinocytes after UVB exposure and suggest that targeting of HuR functions might be crucial for understanding skin cancers caused by aberrant EGF family member-EGFR signaling.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Monoclonal Anti-β-Tubulin I+II antibody produced in mouse, clone JDR.3B8, ascites fluid
Sigma-Aldrich
Amphiregulin human, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture, ≥97% (SDS-PAGE)

Redes sociales

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

Merck

Investigación. Desarrollo. Producción.

Somos un proveedor líder para la industria de Ciencias de la Vida con soluciones y servicios para investigación, desarrollo y producción biotecnológicos, y para desarrollo y producción de tratamientos farmacéuticos

© 2021 Merck KGaA, Darmstadt, Alemania y/o sus filiales. Todos los derechos reservados.

Queda estrictamente prohibida la reproducción sin permiso de cualquiera de los materiales de la página web.