Tumova Sarka, Dolezel David, Jindra Marek
Institute of Entomology, Biology Center of the Czech Academy of Sciences, Ceske Budejovice 37005, Czech Republic.
Institute of Entomology, Biology Center of the Czech Academy of Sciences, Ceske Budejovice 37005, Czech Republic.
J Mol Biol. 2023 Oct 27:168332. doi: 10.1016/j.jmb.2023.168332.
A dozen bHLH-PAS transcription factors have evolved since the dawn of the animal kingdom; nine of them have mutual orthologs between arthropods and vertebrates. These proteins are master regulators in a range of developmental processes from organogenesis, nervous system formation and functioning, to cell fate decisions defining identity of limbs or photoreceptors for color vision. Among the functionally best conserved are bHLH-PAS proteins acting in the animal circadian clock. On the other side of the spectrum are fundamental physiological mechanisms such as those underlying xenobiotic detoxification, oxygen homeostasis, and metabolic adaptation to hypoxia, infection or tumor progression. Predictably, malfunctioning of bHLH-PAS regulators leads to pathologies. Performance of the individual bHLH-PAS proteins is modulated at multiple levels including dimerization and other protein-protein interactions, proteasomal degradation, and by binding low-molecular weight ligands. Despite the vast evolutionary gap dividing arthropods and vertebrates, and the differences in their anatomy, many functions of orthologous bHLH-PAS proteins are remarkably similar, including at the molecular level. Our phylogenetic analysis shows that one bHLH-PAS protein type has been lost during vertebrate evolution. This protein has a unique function as a receptor of the sesquiterpenoid juvenile hormones of insects and crustaceans. Although some other bHLH-PAS proteins are regulated by binding small molecules, the juvenile hormone receptor presents an unprecedented case, since all other non-peptide animal hormones activate members of the nuclear receptor family. The purpose of this review is to compare and highlight parallels and differences in functioning of bHLH-PAS proteins between insects and vertebrates.
自动物王国诞生以来，已经进化出了十二种bHLH-PAS转录因子；其中九种在节肢动物和脊椎动物之间存在共同的直系同源物。这些蛋白质是一系列发育过程中的主要调节因子，从器官发生、神经系统的形成和功能，到决定肢体或彩色视觉光感受器身份的细胞命运决定。在功能上保守性最强的是参与动物生物钟的bHLH-PAS蛋白。而在另一个极端则是一些基本的生理机制，如异源生物解毒、氧稳态以及对缺氧、感染或肿瘤进展的代谢适应等机制。可以预见，bHLH-PAS调节因子的功能失调会导致疾病。单个bHLH-PAS蛋白的性能在多个水平上受到调节，包括二聚化和其他蛋白质-蛋白质相互作用、蛋白酶体降解以及通过结合低分子量配体。尽管节肢动物和脊椎动物之间存在巨大的进化差距，以及它们在解剖结构上的差异，但直系同源bHLH-PAS蛋白的许多功能非常相似，包括在分子水平上。我们的系统发育分析表明，有一种bHLH-PAS蛋白类型在脊椎动物进化过程中丢失了。这种蛋白具有独特的功能，它是昆虫和甲壳类动物倍半萜类保幼激素的受体。虽然其他一些bHLH-PAS蛋白通过结合小分子受到调节，但保幼激素受体却是一个前所未有的例子，因为所有其他非肽类动物激素都是激活核受体家族的成员。这篇综述的目的是比较并突出昆虫和脊椎动物中bHLH-PAS蛋白功能的异同。
