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

eLife

Keit Min Tham¹  Emilie Anne Bard-Chapeau¹  Joanne Chia¹  David James Gill¹  Frederic A Bard¹ 

[1] Institute of Molecular and Cell Biology, Singapore, Singapore;

关键词: golgi;    glycosylation;    cell migration;    COP-I;    retrograde traffic;    endoplasmic reticulum;   

DOI  :  10.7554/eLife.01828

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown