Laurent Audrey, Bihan Réjane, Deschamps Stéphane, Guerrier Daniel, Dupé Valérie, Omilli Francis, Burel Agnès, Pellerin Isabelle
UMR CNRS 6061, Génétique et Développement, IFR 140, Faculté de Médecine, Université de Rennes 1, Campus Villejean, 2 avenue du Professeur Léon Bernard, CS34317, F-35043 Rennes Cedex, France.
Mech Dev. 2007 May;124(5):364-76. doi: 10.1016/j.mod.2007.01.008. Epub 2007 Feb 8.
PBX1 belongs to the TALE-class of homeodomain protein and has a wide functional diversity during development. Indeed, PBX1 is required for haematopoiesis as well as for multiple developmental processes such as skeletal patterning and organogenesis. It has furthermore been shown that PBX1 functions as a HOX cofactor during development. More recent data suggest that PBX1 may act even more broadly by modulating the activity of non-homeodomain transcription factors. To better understand molecular mechanisms triggered by PBX1 during female genital tract development, we searched for additional PBX1 partners that might be involved in this process. Using a two hybrid screen, we identified a new PBX1 interacting protein containing several zinc finger motifs that we called ZFPIP for Zinc Finger PBX1 Interacting Protein. We demonstrated that ZFPIP is expressed in embryonic female genital tract but also in other PBX1 expression domains such as the developing head and the limb buds. We further showed that ZFPIP is able to bind physically and in vivo to PBX1 and moreover, that it prevents the binding of HOXA9/PBX complexes to their consensus DNA site. We suggest that ZFPIP is a new type of PBX1 partner that could participate in PBX1 function during several developmental pathways.
PBX1属于同源异型域蛋白的TALE类，在发育过程中具有广泛的功能多样性。事实上，造血作用以及骨骼模式形成和器官发生等多个发育过程都需要PBX1。此外，研究表明PBX1在发育过程中作为HOX辅因子发挥作用。最近的数据表明，PBX1可能通过调节非同源异型域转录因子的活性发挥更广泛的作用。为了更好地理解PBX1在女性生殖道发育过程中触发的分子机制，我们寻找了可能参与这一过程的其他PBX1结合蛋白。通过双杂交筛选，我们鉴定出一种新的与PBX1相互作用的蛋白，它含有几个锌指基序，我们将其命名为ZFPIP（锌指PBX1相互作用蛋白）。我们证明ZFPIP在胚胎期女性生殖道中表达，也在其他PBX1表达域中表达，如发育中的头部和肢芽。我们进一步表明，ZFPIP能够在体内与PBX1发生物理结合，而且它能阻止HOXA9/PBX复合物与其共有DNA位点结合。我们认为ZFPIP是一种新型的PBX1结合蛋白，可能在多个发育途径中参与PBX1的功能。
