Scuola Normale Superiore, Pisa, Italy.
Crit Rev Biochem Mol Biol. 2010 Feb;45(1):14-22. doi: 10.3109/10409230903365608.
The homeotic proteins are transcription factors, highly conserved in metazoan organisms, exerting a pivotal role in development and differentiation. They individually display a loose specificity for the DNA sequence they can bind, but operate mainly in multi-molecular associations that assure their target and function specificity. Homeotic proteins are known to play a role in the positive or negative regulation of cell proliferation. Furthermore, many homeotic proteins are actually proto-oncogenes, since different translocations involving their genes cause tumors, particularly in the hematopoietic system. A one-hybrid screen to detect proteins with affinity for the lamin B2 replication origin identified three homeotic proteins, namely HoxA13, HoxC10 and HoxC13. Recent data demonstrate that the HoxC13 oncoprotein specifically associates with replication foci and binds in vitro and in vivo to several human DNA replication origins. Moreover, Hox proteins interact with geminin, a regulator of cell cycle progression, and control the interaction of this protein with the DNA replication licensing factor Ctd1. Thus, the homeotic proteins, by participating directly in the function of DNA replication origins, may provide a direct link between the accurate regulation of DNA replication required by the morphogenetic program and the deregulation of this process typical of cancer.
同源异型蛋白是转录因子，在后生动物中高度保守，在发育和分化中发挥关键作用。它们各自对其可以结合的 DNA 序列显示出松散的特异性，但主要在多分子复合物中发挥作用，以确保其靶标和功能的特异性。已知同源异型蛋白在细胞增殖的正或负调控中发挥作用。此外，许多同源异型蛋白实际上是原癌基因，因为涉及它们基因的不同易位会导致肿瘤，特别是在造血系统中。一种用于检测与 lamin B2 复制起点具有亲和力的蛋白质的单杂交筛选鉴定出三种同源异型蛋白，即 HoxA13、HoxC10 和 HoxC13。最近的数据表明，HoxC13 癌蛋白特异性地与复制焦点结合，并在体外和体内与多个人类 DNA 复制起点结合。此外，Hox 蛋白与细胞周期进程调节剂 geminin 相互作用，并控制该蛋白与 DNA 复制许可因子 Ctd1 的相互作用。因此，同源异型蛋白通过直接参与 DNA 复制起点的功能，可能为形态发生程序所需的 DNA 复制的精确调控与癌症中该过程的失调之间提供直接联系。
