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

Chia, J and Tham, KM and Gill, DJ and Bard-Chapeau, EA and Bard, FA (2014) ERK8 is a negative regulator of O-GalNAc glycosylation and cell migration. eLife.

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. Chia et al

Item Type: Article
Additional Information: NIBR author: Bard-Chapeau, EA institute: NIBR- address only contributor address: (Chia, Tham, Gill, Bard-Chapeau, Bard) Institute of Molecular and Cell Biology, Singapore, Singapore (Bard) Department of Biochemistry, National University of Singapore, Singapore, Singapore (Bard-Chapeau) Novartis Institutes for BioMedical Research, Basel, Switzerland
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22651

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