MUC1 activates JNK1 and inhibits apoptosis under genotoxic stress.

Abstract:

:The MUC1 transmembrane glycoprotein is aberrantly overexpressed in diverse human carcinomas and has been shown to inhibit apoptosis induced by genotoxic agents. In the present work, we report that MUC1 binds to and activates JNK1, an important member of the mitogen-activated protein kinases (MAPK) superfamily. The physical interaction between MUC1 cytoplasmic domain (MUC1-CD) and JNK1 was established by GST-pull-down assay in vitro and co-immunoprecipitation assay in vivo. We show that MUC1 activates JNK1 and inhibits cisplatin-induced apoptosis in human colon cancer HCT116 cells. Pharmacological inhibition of JNK or knockdown of JNK significantly reduces the ability of MUC1 to inhibit cisplatin-induced apoptosis. Together, our data indicate that MUC1 can inhibit apoptosis via activating JNK1 pathway in response to genotoxic anticancer agents.

authors

Chen Q,Li D,Ren J,Li C,Xiao ZX

doi

10.1016/j.bbrc.2013.09.055

subject

Has Abstract

pub_date

2013-10-11 00:00:00

pages

179-83

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)01536-2

journal_volume

440

pub_type

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