利用同源盒蛋白中的保守六肽作为同源盒蛋白/前B细胞白血病转录因子相互作用的拮抗剂

Using the Conserved Hexapeptide in HOX Proteins as an Antagonist of HOX/PBX Interactions.

作者信息

Morgan Richard, Smith Christopher, Pandha Hardev

机构信息

School of Medicine and Biosciences, University of West London, London, UK.

Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.

出版信息

Methods Mol Biol. 2025;2889:139-153. doi: 10.1007/978-1-0716-4322-8_10.

DOI:10.1007/978-1-0716-4322-8_10

PMID:39745610

Abstract

The HOX and PBX genes encode transcription factors that have key roles in development and cancer, both independently and as a heterodimer within a complex of proteins that recognizes specific sequences in DNA and can both activate and repress transcription of target genes. Due to functional redundancy amongst HOX proteins, knock down or knock out studies of individual genes often do not result in an altered phenotype. An alternative approach is to target the interaction between HOX and PBX proteins, which is dependent on a conserved hexapeptide region within HOX. To this end, several peptides have been developed based on the hexapeptide sequence which act as competitive antagonists of HOX/PBX binding, including HXR9 and HTL001. Here, we review the methodology that has been used in these studies, including peptide syntheses, cell culture, assays, and mouse models.

摘要

HOX和PBX基因编码转录因子，这些转录因子在发育和癌症中发挥着关键作用，它们既可以独立发挥作用，也可以作为蛋白质复合物中的异二聚体发挥作用，该蛋白质复合物能够识别DNA中的特定序列，并可以激活和抑制靶基因的转录。由于HOX蛋白之间存在功能冗余，对单个基因进行敲低或敲除研究通常不会导致表型改变。另一种方法是靶向HOX和PBX蛋白之间的相互作用，这种相互作用依赖于HOX内保守的六肽区域。为此，已经基于六肽序列开发了几种肽，它们作为HOX/PBX结合的竞争性拮抗剂，包括HXR9和HTL001。在这里，我们回顾了这些研究中使用的方法，包括肽合成、细胞培养、检测和小鼠模型。