c-Jun regulates phosphoinositide-dependent kinase 1 transcription: implication for Akt and protein kinase C activities and melanoma tumorigenesis

• Autores: Lopez Bergami, Pablo Roberto; Kim, Hyungsoo; Dewing, Antimone; Goydos, James; Aaronson, Stuart; Ronai, Ze´ev
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: MELANOMA; CANCER; GENE EXPRESSION REGULATION; NEOPLASM TRANSPLANTATION
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

utations in N-RAS and B-RAF, which commonly occur in melanomas, result in constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling. Active ERK increases expression and activity of the c-Jun transcription factor, linking ERK and Jun N-terminal kinase (JNK) cascades. Here, we show that c-Jun regulates transcription of phosphoinositide-dependent kinase 1 (PDK1) with a concomitant impact on Akt and protein kinase C (PKC) activity and related substrates. Inhibition of c-Jun reduces PDK1 expression and attenuates Akt and PKC activity, which can be restored by exogenous PDK1. c-Jun regulation of PDK1 in melanoma contributes to growth rate and the ability to form tumors in mice. Correspondingly, increased levels of c-Jun in melanoma cell lines coincide with up-regulation of PDK1 and phosphorylation of PKC and Akt. The identification of c-Jun as a transcriptional regulator of PDK1 expression highlights key mechanisms underlying c-Jun oncogenic activity, and provides new insight into the nature of up-regulated Akt and PKC in melanoma.
Fil: Lopez Bergami, Pablo Roberto. The Burnham Institute for Medical Research; Estados Unidos. Mount Sinai School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
Fil: Kim, Hyungsoo . The Burnham Institute for Medical Research; Estados Unidos
Fil: Dewing, Antimone . The Burnham Institute for Medical Research; Estados Unidos
Fil: Goydos, James . Robert Wood Johnson Medical School; Estados Unidos
Fil: Aaronson, Stuart. Mount Sinai School of Medicine; Estados Unidos
Fil: Ronai, Ze´ev. The Burnham Institute for Medical Research; Estados Unidos