Abstract
BackgroundThe Cancer-Testis antigens (CTA) are proteins expressed in human germ line and certain cancer cells. CTAs form a large gene family, representing 10% of X-chromosomal genes. They have high potential for cancer-specific immunotherapy. However, their biological functions are currently unknown. Prostate associated genes (PAGE) are characterized as CTAs. PAGE5 is one of six proteins belonging to this protein family, also called CT16.Methodology/Principal findingsIn this study we show, using bioinformatics, chromatographic and solution state NMR spectroscopic methods, that PAGE5 is an intrinsically disordered protein (IDP).Conclusion/SignificanceThe study stands out as the first time structural characterization of the PAGE family protein and introduces how solution state NMR spectroscopy can be effectively utilized for identification of molecular recognition regions (MoRF) in IDPs, known often as transiently populated secondary structures.
Highlights
The Cancer-Testis antigens (CTAs) are expressed mainly in normal human trophoblasts and germ line i.e. testis and placenta, but not in other healthy cells [1]
PAGE5 has been recognized as potential marker for diagnosis of specific cancers as increased expression levels are observed in melanoma, renal and lung cancer cells [4,16,17]
Since molecular weight of monomeric PAGE5 is only 11 kDa, SEC gave an estimation of four times larger MW, i.e. tetrameric protein
Summary
The Cancer-Testis antigens (CTAs) are expressed mainly in normal human trophoblasts and germ line i.e. testis and placenta, but not in other healthy cells [1]. Prostate associated genes (PAGEs) together with their sequentially homologous proteins, X antigens (XAGEs) and G antigens (GAGEs), are members of GAGE gene family products [11]. Exact biological functions of these proteins, either in prostate or cancer, remain to be characterized, recent studies have highlighted anti-apoptotic properties for PAGE4 [12] and GAGE7 [13]. There are six different PAGE proteins (PAGE1, 2, 2B, 3, 4, and 5) [11,14,15], expressed in prostate or testis and in several cancer cells. The Cancer-Testis antigens (CTA) are proteins expressed in human germ line and certain cancer cells. CTAs form a large gene family, representing 10% of X-chromosomal genes They have high potential for cancer-specific immunotherapy. PAGE5 is one of six proteins belonging to this protein family, called CT16
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