Yang R Y, Hsu D K, Yu L, Ni J, Liu F T
La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
J Biol Chem. 2001 Jun 8;276(23):20252-60. doi: 10.1074/jbc.M010914200. Epub 2001 Mar 30.
Galectins are a family of beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains (CRDs). Here we report the identification and characterization of a new galectin, galectin-12, which contains two domains that are homologous to the galectin CRD. The N-terminal domain contains all of the sequence elements predicted to form the two beta-sheets found in other galectins, as well as conserved carbohydrate-interacting residues. The C-terminal domain shows considerable divergence from the consensus sequence, and many of these conserved residues are not present. Nevertheless, the protein has lactose binding activity, most likely due to the contribution of the N-terminal domain. The mRNA for galectin-12 contains features coding for proteins with growth-regulatory functions. These include start codons in a context that are suboptimal for translation initiation and AU-rich motifs in the 3'-untranslated region, which are known to confer instability to mRNA. Galectin-12 mRNA is sparingly expressed or undetectable in many tissues and cell lines tested, but it is up-regulated in cells synchronized at the G(1) phase or the G(1)/S boundary of the cell cycle. Ectopic expression of galectin-12 in cancer cells causes cell cycle arrest at the G(1) phase and cell growth suppression. We conclude that galectin-12 is a novel regulator of cellular homeostasis.
半乳糖凝集素是一类具有保守碳水化合物识别结构域（CRD）的β-半乳糖苷结合动物凝集素。在此，我们报告了一种新的半乳糖凝集素——半乳糖凝集素-12的鉴定与特征，它含有两个与半乳糖凝集素CRD同源的结构域。N端结构域包含所有预测会形成其他半乳糖凝集素中发现的两个β折叠的序列元件，以及保守的碳水化合物相互作用残基。C端结构域与共有序列有相当大的差异，许多这些保守残基不存在。然而，该蛋白具有乳糖结合活性，很可能是由于N端结构域的作用。半乳糖凝集素-12的mRNA包含编码具有生长调节功能蛋白质的特征。这些特征包括起始密码子所处的翻译起始环境欠佳，以及3'非翻译区富含AU的基序，已知这些会使mRNA不稳定。在许多测试的组织和细胞系中，半乳糖凝集素-12的mRNA表达稀少或无法检测到，但在细胞周期G1期或G1/S边界同步化的细胞中会上调。半乳糖凝集素-12在癌细胞中的异位表达导致细胞周期停滞在G1期并抑制细胞生长。我们得出结论，半乳糖凝集素-12是细胞稳态的一种新型调节因子。
