Author/Authors :
Lopez-Bergami، نويسنده , , Pablo and Huang، نويسنده , , Conway and Goydos، نويسنده , , James S. and Yip، نويسنده , , Dana and Bar-Eli، نويسنده , , Menashe and Herlyn، نويسنده , , Meenhard and Smalley، نويسنده , , Keiran S.M. and Mahale، نويسنده , , Alka and Eroshkin، نويسنده , , Alexey and Aaronson، نويسنده , , Stuart and Ronai، نويسنده , , Zeʹev، نويسنده ,
Abstract :
Summary
tutive activation of MEK-ERK signaling is often found in melanomas. Here, we identify a mechanism that links ERK with JNK signaling in human melanoma. Constitutively active ERK increases c-Jun transcription and stability, which are mediated by CREB and GSK3, respectively. Subsequently, c-Jun increases transcription of target genes, including RACK1, an adaptor protein that enables PKC to phosphorylate and enhance JNK activity, enforcing a feed-forward mechanism of the JNK-Jun pathway. Activated c-Jun is also responsible for elevated cyclin D1 expression, which is frequently overexpressed in human melanoma. Our data reveal that, in human melanoma, the rewired ERK signaling pathway upregulates JNK and activates the c-Jun oncogene and its downstream targets, including RACK1 and cyclin D1.
