GP73, a novel Golgi-localized protein upregulated by viral infection

Abstract

We report the isolation and characterization of GP73, a novel 73kDa human Golgi protein. 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. 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. Northern blot analysis of RNA from multiple human tissues reveals a single GP73 mRNA transcript with a size of approximately 3.0kb. Immunohistochemical studies using rabbit polyclonal antisera directed against recombinant GP73 demonstrate that the protein is preferentially expressed by epithelial cells in many human tissues. In normal livers, GP73 is consistently present in biliary epithelial cells, whereas hepatocytes show little or no signal. In contrast, livers of patients with GCH display strong GP73 immunoreactivity in multinucleated hepatocytes. GP73 mRNA and protein are expressed in highly differentiated HepG2 hepatoma cells after infection with adenovirus in vitro. We conclude that GP73 represents a novel, epithelial cell-specific integral membrane Golgi protein that can be upregulated in response to viral infection.

Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases

“…When viral or nonviral etiologies bring about acute or chronic hepatitis, GP73 is expressed in the majority of hepatocytes. In chronic liver diseases, GP73 protein and mRNA expression increases gradually, not only in the hepatocytes, but also in activated stellate cells, 7,8,10 commonly considered the most important cell type involved in hepatic fibrogenesis. 29 Therefore maximal GP73 expressions are seen in fully established cirrhosis.…”

“…5,6 GP73, a 73 kd resident type II Golgi transmembrane protein is a potential member of this group. 7 In normal livers, GP73 is constitutively expressed by biliary epithelial cells, but only minimally by hepatocytes. 8,9 Hepatocellular expression of GP73 mRNA and protein is dramatically upregulated in acute or chronic hepatitis, regardless of the etiology, and accompanies the advanced fibrogenesis stage.…”

GOLPH2 protein expression as a novel tissue biomarker for prostate cancer: implications for tissue-based diagnostics

“…GOLPH2 is a 73-kDa Golgi apparatus-associated protein coded by the gene GOLM1 located on chromosome 9q21.33 and was originally cloned from a library derived from liver tissue of a patient with adult giant-cell hepatitis (Kladney et al, 2000). The initial report also described GOLPH2 expression in a variety of other human tissues at RNA and protein level and demonstrated colocalisation of GOLPH2 with giantin, a type II Golgi membrane protein located at the cis and medial Golgi compartment.…”

“…GOLPH2 is a Golgi phosphoprotein of yet unknown function that has until very recently only been described in liver disease as a potential serum marker of hepatocellular carcinoma (Kladney et al, 2000(Kladney et al, , 2002aIftikhar et al, 2004;Marrero et al, 2005;Bachert et al, 2007). GOLPH2 mRNA has recently been described as an integral part of a multiplex marker to detect prostate cancer from urine samples that even outperformed a prostate-specific antigen (PSA) blood test (Laxman et al, 2008).…”

Serum Golgi Phosphoprotein 2 level: A better marker than alpha-fetoprotein for diagnosing early hepatocellular carcinoma

“…GOLPH2 was originally described as a resident Golgi type II transmembrane protein expressed primarily in epithelial cells of many human tissues. 2 In the normal human liver, GOLPH2 expression was found in biliary epithelial cells, but it was barely detectable in hepatocytes. However, expression of GOLPH2 was found to be strongly upregulated in hepatocytes from patients with viral and nonviral liver diseases.…”