Cloning and characterization of human Golgi phosphoprotein 2 gene (GOLPH2/GP73/GOLM1) promoter

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• 作者：Yu Gong¹ ; Qi Long¹ ; Hongbin Xie ; Tianyu Zhang ; Tao Peng ; ^{peng_tao@gibh.ac.cn}
• 关键词：GOLPH2 ; Golgi phosphoprotein 2 ; HCC ; hepatocellular carcinoma ; CR ; conserved region ; CtBP ; c-terminal binding protein ; CID ; CtBP interaction domain ; E1A ; early region 1A ; Sp1 ; specificity protein 1 ; GAPDH ; glyceraldehyde 3-phosphate dehydrogenase
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：18 May, 2012
• 卷：421
• 期：4
• 页码：713-720
• 文件大小：418 K

摘要

Human Golgi phosphoprotein 2 gene (also known as GOLPH2, GP73 or GOLM1) encodes an epithelial-specific Golgi membrane protein which can be induced by virus infection. It is also overexpressed in a number of tumors and is currently considered as an early diagnosis marker for hepatocellular carcinoma. However, little is known about how GOLPH2 is dysregulated in these disease conditions and the functional implications of its overexpression. The aim of this study is to investigate human GOLPH2 regulation mechanisms. We cloned a 2599 bp promoter fragment of GOLPH2 and found it maintained epithelial specificity. By deletion analysis, a repressive region (鈭?64 to 鈭?34 bp), a positive regulatory region (鈭?34 to 鈭?21 bp) and a core promoter region (鈭?21 to 鈭?9 bp) were identified. Sequence analysis revealed that GOLPH2 core promoter was devoid of canonical TATA element and classified as a TATA-less promoter. Adenoviral early region 1A (E1A) was able to activate GOLPH2 and the CtBP interaction domain of E1A was sufficient but not required for activation. A GC-box motif (鈭?9 to 鈭?3 bp) in GOLPH2 core promoter region partly mediated E1A transactivation. These results delineated regulatory regions and functional element in GOLPH2 promoter, elucidated adenoviral E1A stimulation mechanisms and provided insight into GOLPH2 functions.