Golgi membrane protein GP73 modified-liposome mediates the antitumor effect of survivin promoter-driven HSVtk in hepatocellular carcinoma

The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are highly conserved regulators of membrane dynamics and protein trafficking. The interactions of large ARF GEFs with cellular membranes for localization and/or activation are likely to participate in regulated recruitment of ARF and effectors. However, these interactions remain largely unknown. Here we characterize Gmh1p, the first Golgi transmembrane-domain partner of any of the high-molecular-weight ARF-GEFs. Gmh1p is an evolutionarily conserved protein. We demonstrate molecular interaction between the yeast Gmh1p and the large ARF-GEFs Gea1p and Gea2p. This interaction involves a domain of Gea1p and Gea2p that is conserved in the eukaryotic orthologues of the Gea proteins. A single mutation in a conserved amino acid residue of this domain is sufficient to abrogate the interaction, whereas the overexpression of Gmh1p can compensate in vivo defects caused by mutations in this domain. We show that Gmh1p is an integral membrane protein that localizes to the early Golgi in yeast and in human HeLa cells and cycles through the ER. Hence, we propose that Gmh1p acts as a positive Golgi-membrane partner for Gea function. These results are of general interest given the evolutionary conservation of both ARF-GEFs and the Gmh proteins.

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Mouse Prenylated Rab Acceptor Is a Novel Golgi Membrane Protein

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.2000.3316 ◽

2000 ◽

Vol 275 (2) ◽

pp. 509-516 ◽

Cited By ~ 12

Author(s):

Zhimin Liang ◽

Guangpu Li

Keyword(s):

Membrane Protein ◽

Golgi Membrane

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Triclosan treatment decreased the antitumor effect of sorafenib on hepatocellular carcinoma cells

OncoTargets and Therapy ◽

10.2147/ott.s165436 ◽

2018 ◽

Vol Volume 11 ◽

pp. 2945-2954 ◽

Cited By ~ 6

Author(s):

Man Wu ◽

Guanren Zhao ◽

Xiaomei Zhuang ◽

Tianhong Zhang ◽

Ce Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Antitumor Effect ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells

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Prebiotics: A Novel Approach to Treat Hepatocellular Carcinoma

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2017/6238106 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Naz Fatima ◽

Tasleem Akhtar ◽

Nadeem Sheikh

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Antitumor Effect ◽

Gut Permeability ◽

Gut Flora ◽

Effective Barrier ◽

The Third ◽

Oncogenic Pathways ◽

Novel Approach ◽

Genetic Modifications

Hepatocellular carcinoma is one of the fatal malignancies and is considered as the third leading cause of death. Mutations, genetic modifications, dietary aflatoxins, or impairments in the regulation of oncogenic pathways may bring about liver cancer. An effective barrier against hepatotoxins is offered by gut-liver axis as a change in gut permeability and expanded translocation of lipopolysaccharides triggers the activation of Toll-like receptors which stimulate the process of hepatocarcinogenesis. Prebiotics, nondigestible oligosaccharides, have a pivotal role to play when it comes to inducing an antitumor effect. A healthy gut flora balance is imperative to downregulation of inflammatory cytokines and reducing lipopolysaccharides induced endotoxemia, thus inducing the antitumor effect.

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Thermosensitive Injectable Hydrogel Enhances the Antitumor Effect of Embelin in Mouse Hepatocellular Carcinoma

Journal of Pharmaceutical Sciences ◽

10.1002/jps.23885 ◽

2014 ◽

Vol 103 (3) ◽

pp. 965-973 ◽

Cited By ~ 10

Author(s):

Meiyu Peng ◽

Shuxin Xu ◽

Yong Zhang ◽

Lijuan Zhang ◽

Bingqing Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Antitumor Effect ◽

Injectable Hydrogel

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The yeast VPS5/GRD2 gene encodes a sorting nexin-1-like protein required for localizing membrane proteins to the late Golgi

Journal of Cell Science ◽

10.1242/jcs.110.9.1063 ◽

1997 ◽

Vol 110 (9) ◽

pp. 1063-1072 ◽

Cited By ~ 7

Author(s):

S.F. Nothwehr ◽

A.E. Hindes

Keyword(s):

Membrane Proteins ◽

Membrane Protein ◽

Protein Localization ◽

Endocytic Pathway ◽

Yeast Cells ◽

Carboxypeptidase Y ◽

Golgi Membrane ◽

Sorting Nexin ◽

Vacuolar Protein ◽

Sorting Nexin 1

Genetic analysis of late Golgi membrane protein localization in Saccharomyces cerevisiae has uncovered a large number of genes (called GRD) that are required for retention of A-ALP, a model late Golgi membrane protein. Here we describe one of the GRD genes, VPSS/GRD2, that encodes a hydrophilic protein similar to human sorting nexin-1, a protein involved in trafficking of the epidermal growth factor receptor. In yeast cells containing a vps5 null mutation the late Golgi membrane proteins A-ALP and Kex2p were rapidly mislocalized to the vacuolar membrane. A-ALP was delivered to the vacuole in vps5 mutants in a manner independent of a block in the early endocytic pathway. vps5 null mutants also exhibited defects in both vacuolar morphology and in sorting of a soluble vacuolar protein, carboxypeptidase Y. The latter defect is apparently due to an inability to localize the carboxypeptidase Y sorting receptor, Vps10p, to the Golgi since it is rapidly degraded in the vacuole in vps5 mutants. Fractionation studies indicate that Vps5p is distributed between a free cytosolic pool and a particulate fraction containing Golgi, transport vesicles, and possibly endosomes, but lacking vacuolar membranes. Immunofluorescence microscopy experiments show that the membrane-associated pool of Vps5p localizes to an endosome-like organelle that accumulates in the class E vps27 mutant. These results support a model in which Vps5p is required for retrieval of membrane proteins from a prevacuolar/late endosomal compartment back to the late Golgi apparatus.

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