Disease relevance of GOLPH2

• Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease [1].
• GP73 expression in vitro was studied by Western blotting and immunofluorescence microscopy in HepG2 and SK-Hep-1 cells and in the HepG2-derived, hepatitis B virus (HBV)-transfected HepG2215 and HepG2T14.1 cell lines [1].
• Mapping studies using a panel of mutant adenoviruses demonstrated that the E1A C-terminus, specifically its CtBP interaction domain (CID), is required for GP73 expression [2].
• Here we report that GP73 is induced at the RNA and protein level in human Hep3B hepatoma cells infected by human Ad5 and Ad2 [2].
• The potential of this technology for biomarker discovery and the implications of increased levels of GP73 in liver cancer are discussed [3].

High impact information on GOLPH2

• One such glycoprotein, Golgi Protein 73 (GP73), was found to be elevated and hyperfucosylated in animals with HCC [3].
• In SK-Hep-1 cells, GP73 expression was increased in response to interferon gamma (IFN-gamma), and inhibited by tumor necrosis factor alpha (TNF-alpha) [1].
• In conclusion, increased expression of GP73 in hepatocytes appears to be a general feature of advanced liver disease, and may be regulated via distinct pathways that involve hepatotropic viruses or cytokines [1].
• The aims of the present study were to compare GP73 protein levels in viral and nonviral human liver disease and in normal livers, to identify its cellular sources, and to study the regulation of its expression in hepatoma cells in vitro [1].
• In normal livers, GP73 was constitutively expressed by biliary epithelial cells but not by hepatocytes [1].

Biological context of GOLPH2

• Upregulation of the Golgi protein GP73 by adenovirus infection requires the E1A CtBP interaction domain [2].
• The GP73 cDNA was cloned by differential screening of a cDNA library derived from the liver of a patient with adult giant-cell hepatitis (GCH), a rare form of hepatitis with presumed viral etiology [4].

Anatomical context of GOLPH2

• GP73 was present at high levels in HepG2215 cells (a cell line that supports active HBV replication), but was absent in HepG2T14.1 cells (an HBV-transfected cell line that does not support HBV replication) and in HBV-free HepG2 cells [1].
• GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis (Gene 2000;249:53-65) [1].
• Nevertheless, after pH disruption by monensin, GPP130 and GP73 redistributed to endosomes containing redistributed TGN38/46, but not other endosomal markers [5].
• GP73 and liver disease: a (Golgi) complex enigma [6].

Associations of GOLPH2 with chemical compounds

• Unlike the TGN marker TGN38/46, GPP130 and GP73 colocalized in the early Golgi and redistributed to the ER after brefeldin A treatment [5].
• GP73 had a sensitivity of 69% and a specificity of 75% at the optimal cutoff point of 10 relative units, with an area under the receiver operating curve of 0.79 vs. 0.61 for AFP (P = 0.001) [7].

Other interactions of GOLPH2

• Although GP73 did not associate with GPP130, its steady-state Golgi targeting was also mediated by a lumenal predicted coiled-coil stem domain [5].
• GP73 expression was measured by RNase protection assay, immunoblotting, or immunofluorescence microscopy [2].
• In vitro transcription-translation studies indicate that GP73 is an integral membrane protein, and immunolocalization experiments using epitope-tagged GP73 demonstrate that the protein is localized to the Golgi apparatus [4].

Analytical, diagnostic and therapeutic context of GOLPH2

• Northern blot analysis of RNA from multiple human tissues reveals a single GP73 mRNA transcript with a size of approximately 3.0kb [4].

References