Glycosyltransferase-specific Golgi-targeting Mechanisms

Petrosyan, Armen; Ali, Mir A.; Cheng, Pi Wan

doi:10.1074/jbc.c112.403006

Cited by 47 publications

(73 citation statements)

References 37 publications

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“…2G,H). These data are consistent with previous reports from Golgb1 (giantin) knockdown studies in tissue culture cells showing that Golgb1 is not required for Golgi structural integrity (Petrosyan et al, 2012(Petrosyan et al, , 2014Puthenveedu and Linstedt, 2001;Wong and Munro, 2014).…”

Section: G179ssupporting

confidence: 83%

“…In particular, siRNA knockdown studies suggest that the C2GnT-M and C2GnT-L synthases in the O-glycosylation pathway use Golgb1 exclusively to target to Golgi membrane, whereas C1GalT1 and ST3Gal1 synthases use Golgb1 and GM130-Grasp65 (also known as Gorasp1) as alternative docking sites (Petrosyan et al, 2012(Petrosyan et al, , 2014Wong and Munro, 2014). O-glycosylation in the Golgi starts with synthesis of the glycoconjugate GalNAc-α1-O-Ser/Thr, known as the Tn antigen.…”

Section: Golgb1 Plays An Important Role In Protein Glycosylationmentioning

confidence: 99%

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Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

et al. 2016

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Cleft palate is a common major birth defect for which currently known causes account for less than 30% of pathology in humans. In this study, we carried out mutagenesis screening in mice to identify new regulators of palatogenesis. Through genetic linkage mapping and whole exome sequencing, we identified a loss-of-function mutation in the Golgb1 gene that co-segregated with cleft palate in a new mutant mouse line. Golgb1 encodes a ubiquitously expressed large coiled-coil protein, known as giantin, that is localized at the Golgi membrane. Using CRISPR/Cas9-mediated genome editing, we generated and analyzed developmental defects in mice carrying additional Golgb1 loss-of-function mutations, which validated a critical requirement for Golgb1 in palate development. Through maxillary explant culture assays, we demonstrate that the Golgb1 mutant embryos have intrinsic defects in palatal shelf elevation. Just prior to the developmental stage of palatal shelf elevation in the wildtype littermates, Golgb1 mutant embryos exhibit increased cell density, reduced hyaluronan accumulation, and impaired protein glycosylation in the palatal mesenchyme. Together, these results demonstrate that, although it is a ubiquitously expressed Golgi-associated protein, Golgb1 has specific functions in protein glycosylation and tissue morphogenesis.

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Section: G179ssupporting

confidence: 83%

Section: Golgb1 Plays An Important Role In Protein Glycosylationmentioning

confidence: 99%

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

et al. 2016

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“…Subsequently, the receptor redirects these proteins back to the ER as part of the anterograde transport (Pfeffer, 2007;Capitani and Sallese, 2009). Several other proteins, like the glycosyltransferases, translocate to the Golgi owing to their interaction with Golgitargeting domains of other proteins or by interacting with various golgins, such as GM130, Giantin, and GRASP55 and GRASP65 (Petrosyan et al, 2012). Additionally, some of the Golgi proteins seem to have specific targeting sequence and domains, distinct from the classical KDEL (Kjer-Nielsen et al, 1999;Lee and Pohajdak, 2000;Brown et al, 2001;Shi et al, 2004), with the exact sequences and their common mechanism of action still, as yet, obscure.…”

Section: Discussionmentioning

confidence: 99%

Mitotic Golgi translocation of ERK1c is mediated by PI4KIIIβ/14-3-3γ shuttling complex

Wortzel

Hanoch

Porat

et al. 2015

Journal of Cell Science

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Golgi fragmentation is a highly regulated process that allows division of the Golgi complex between the two daughter cells. The mitotic reorganization of the Golgi is accompanied by a temporary block in Golgi functioning, as protein transport in and out of the Golgi stops. Our group has previously demonstrated the involvement of the alternatively spliced variants ERK1c and MEK1b (ERK1 is also known as MAPK3, and MEK1 as MAP2K1) in mitotic Golgi fragmentation. We had also found that ERK1c translocates to the Golgi at the G2 to M phase transition, but the molecular mechanism underlying this recruitment remains unknown. In this study, we narrowed the translocation timing to prophase and prometaphase, and elucidated its molecular mechanism. We found that CDK1 phosphorylates Ser343 of ERK1c, thereby allowing the binding of phosphorylated ERK1c to a complex that consists of PI4KIIIβ (also known as PI4KB) and the 14-3-3γ dimer (encoded by YWHAB). The stability of the complex is regulated by protein kinase D (PKD)-mediated phosphorylation of PI4KIIIβ. The complex assembly induces the Golgi shuttling of ERK1c, where it is activated by MEK1b, and induces Golgi fragmentation. Our work shows that protein shuttling to the Golgi is not completely abolished at the G2 to M phase transition, thus integrating several independent Golgiregulating processes into one coherent pathway.

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“…Core 1 b1,3-galactosyltransferase (C1GALT1) is a critical mucin-type O-glycosyltransferase that is localized in the Golgi apparatus (19,20). C1GALT1 transfers galactose (Gal) to Nacetylgalactosamine (GalNAc) to a serine (Ser) or threonine (Thr) residue (Tn antigen) to form the Galb1-3GalNAca1-Ser/ Thr structure (T antigen or core 1 structure; ref.…”

Section: Introductionmentioning

confidence: 99%

C1GALT1 Enhances Proliferation of Hepatocellular Carcinoma Cells via Modulating MET Glycosylation and Dimerization

Liu

Huang

et al. 2013

Cancer Research

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Altered glycosylation is a hallmark of cancer. The core 1 b1,3-galactosyltransferase (C1GALT1) controls the formation of mucin-type O-glycans, far overlooked and underestimated in cancer. Here, we report that C1GALT1 mRNA and protein are frequently overexpressed in hepatocellular carcinoma tumors compared with nontumor liver tissues, where it correlates with advanced tumor stage, metastasis, and poor survival. Enforced expression of C1GALT1 was sufficient to enhance cell proliferation, whereas RNA interferencemediated silencing of C1GALT1 was sufficient to suppress cell proliferation in vitro and in vivo. Notably, C1GALT1 attenuation also suppressed hepatocyte growth factor (HGF)-mediated phosphorylation of the MET kinase in hepatocellular carcinoma cells, whereas enforced expression of C1GALT1 enhanced MET phosphorylation. MET blockade with PHA665752 inhibited C1GALT1-enhanced cell viability. In support of these results, we found that the expression level of phospho-MET and C1GALT1 were associated in primary hepatocellular carcinoma tissues. Mechanistic investigations showed that MET was decorated with O-glycans, as revealed by binding to Vicia villosa agglutinin and peanut agglutinin. Moreover, C1GALT1 modified the O-glycosylation of MET, enhancing its HGF-induced dimerization and activation. Together, our results indicate that C1GALT1 overexpression in hepatocellular carcinoma activates HGF signaling via modulation of MET O-glycosylation and dimerization, providing new insights into how O-glycosylation drives hepatocellular carcinoma pathogenesis. Cancer Res; 73(17); 5580-90. Ó2013 AACR.

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Glycosyltransferase-specific Golgi-targeting Mechanisms

Cited by 47 publications

References 37 publications

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

Mitotic Golgi translocation of ERK1c is mediated by PI4KIIIβ/14-3-3γ shuttling complex

C1GALT1 Enhances Proliferation of Hepatocellular Carcinoma Cells via Modulating MET Glycosylation and Dimerization

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