GALNT6 Stabilizes GRP78 Protein by O-glycosylation and Enhances its Activity to Suppress Apoptosis Under Stress Condition.

Abstract:

:We previously reported that overexpression of an O-type glycosyltransferase, GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) played critical roles in mammary carcinogenesis. To further investigate the biological function of GALNT6, we screened a substrate protein(s) of GALNT6 using a VVA (Vicia villosa agglutinin) lectin (specific to GalNAc-Ser/Thr) pull-down method followed by mass spectrometry analysis. Here we report GRP78 (glucose-regulated protein 78, also known as HSPA5, heat shock 70 kDa protein 5), which is highly expressed in cancer cells and indicated to play important roles in various cellular processes including ER (endoplasmic reticulum) stress and autophagy, as a novel substrate of GALNT6. We found that GALNT6-induced O-glycosylation is critical for the stability of GRP78, its subcellular localization in ER, and its anti-apoptotic function. Furthermore, we demonstrated that overexpression of GRP78 could be important for Golgi-to-ER relocation of GALNT6. Collectively, our study revealed biological significances of O-glycosylation of GRP78 protein, which might play significant roles in the survival of cancer cells, and thus provided a new insight in cancer cell death and useful information for development of anti-cancer treatment targeting the GALNT6-GRP78 pathway.

journal_name

Neoplasia

authors

Lin J,Chung S,Ueda K,Matsuda K,Nakamura Y,Park JH

doi

10.1016/j.neo.2016.11.007

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

43-53

issue

1

eissn

1522-8002

issn

1476-5586

pii

S1476-5586(16)30192-0

journal_volume

19

pub_type

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