ERK8 is a negative regulator of O-GalNAc glycosylation and cell migration

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ERK8 is a negative regulator of O-GalNAc glycosylation and cell migration
Title:
ERK8 is a negative regulator of O-GalNAc glycosylation and cell migration
Journal Title:
eLife
Keywords:
Publication Date:
11 March 2014
Citation:
Abstract:
ER O-glycosylation can be induced through relocalisation GalNAc-Transferases from the Golgi. This process markedly stimulates cell migration and is constitutively activated in more than 60% of breast carcinomas. How this activation is achieved remains unclear. Here, we screened 948 signalling genes using RNAi and imaging. We identified 12 negative regulators of O-glycosylation that all control GalNAc-T sub-cellular localisation. ERK8, an atypical MAPK with high basal kinase activity, is a strong hit and is partially localised at the Golgi. Its inhibition induces the relocation of GalNAc-Ts, but not of KDEL receptors, revealing the existence of two separate COPI-dependent pathways. ERK8 down-regulation, in turn, activates cell motility. In human breast and lung carcinomas, ERK8 expression is reduced while ER O-glycosylation initiation is hyperactivated. In sum, ERK8 appears as a constitutive brake on GalNAc-T relocalisation, and the loss of its expression could drive cancer aggressivity through increased cell motility. - See more at: http://elifesciences.org/content/3/e01828#sthash.3u6WQ39U.dpuf
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
Description:
ISSN:
2050-084X
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