The classical function of human chorionic gonadotropin (hCG) is its role in supporting pregnancy. hCG is a dimer consisting of two highly glycosylated subunits, alpha (CGA) and beta (CGB). The beta-hCG protein is encoded by CGB3, CGB5, CGB7 and CGB8 genes. CGB3, 5 and 8 code for an identical protein, CGB3/5/8, whereas CGB7 differs in three amino acids from CGB3/5/8. We had observed earlier that CGB7 and CGB3/5/8 display very distinct tissue expression patterns and that the tumor suppressor and transcription factor p53 can activate expression of CGB7 but not of CGB3/5/8 genes. Here, we investigate the glycan structures and possible functional differences of the two CGB variants. To this end, we established a system to produce and isolate recombinant CGA, CGB7 and CGB3/5/8 proteins. We found that N- and O-glycosylation patterns of CGB7 and CGB3/5/8 are quite similar. Functional assays were performed by testing activation of the ERK1/2 pathway and demonstrated that CGB7 and CGB5/5/8 appear to be functionally redundant isoforms, although a slight difference in the kinetics of ERK1/2 pathway activation was observed. This is the first time that biological activity of CGB7 is shown. In summary, the results lead to the hypothesis that CGB7 and CGB3/5/8 do not hold significant functional differences but that timing and cell type of their expression is the key for understanding their divergent evolution.

人绒毛膜促性腺激素 (hCG) 的经典功能是其支持怀孕的作用。hCG 是一种二聚体，由两个高度糖基化的亚基 alpha (CGA) 和 beta (CGB) 组成。β-hCG 蛋白由CGB3、CGB5、CGB7和CGB8基因编码。CGB3，5和8为一个相同的蛋白质编码，CGB3 / 5/8，而在三个不同CGB7氨基从CGB3 / 5/8的酸。我们之前观察到 CGB7 和 CGB3/5/8 显示出非常不同的组织表达模式，并且肿瘤抑制因子和转录因子 p53 可以激活CGB7 的表达，但不能激活CGB3/5/8基因。在这里，我们研究了两种 CGB 变体的聚糖结构和可能的功能差异。为此，我们建立了一个系统来生产和分离重组 CGA、CGB7 和 CGB3/5/8 蛋白。我们发现 CGB7 和 CGB3/5/8 的 N-和 O-糖基化模式非常相似。通过测试 ERK1/2 通路的激活进行功能测定，并证明 CGB7 和 CGB5/5/8 似乎是功能冗余的同种型，尽管观察到 ERK1/2 通路激活的动力学略有不同。这是首次显示 CGB7 的生物活性。总之，结果导致假设 CGB7 和 CGB3/5/8 没有显着的功能差异，但它们表达的时间和细胞类型是理解它们不同进化的关键。