Curt Jesús R, Martín Paloma, Foronda David, Hudry Bruno, Kannan Ramakrishnan, Shetty Srividya, Merabet Samir, Saurin Andrew J, Graba Yacine, Sánchez-Herrero Ernesto
Centro de Biología Molecular Severo Ochoa (CBM), CSIC-UAM, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Departamento de Medicina, Facultad de Ciencias Biomédicas y de la Salud, Universidad Europea de Madrid, Madrid, Spain.
PLoS Genet. 2025 Jan 13;21(1):e1011355. doi: 10.1371/journal.pgen.1011355. eCollection 2025 Jan.
Hox proteins, a sub-group of the homeodomain (HD) transcription factor family, provide positional information for axial patterning in development and evolution. Hox protein functional specificity is reached, at least in part, through interactions with Pbc (Extradenticle (Exd) in Drosophila) and Meis/Prep (Homothorax (Hth) in Drosophila) proteins. Most of our current knowledge of Hox protein specificity stems from the study of anterior and central Hox proteins, identifying the molecular and structural bases for Hox/Pbc/Meis-Prep cooperative action. Posterior Hox class proteins, Abdominal-B (Abd-B) in Drosophila and Hox9-13 in vertebrates, have been comparatively less studied. They strongly diverge from anterior and central class Hox proteins, with a low degree of HD sequence conservation and the absence of a core canonical Pbc interaction motif. Here we explore how Abd-B function interface with that of Exd/Hth using several developmental contexts, studying mutual expression control, functional dependency and intrinsic protein requirements. Results identify cross-regulatory interactions setting relative expression and activity levels required for proper development. They also reveal organ-specific requirement and a binary functional interplay with Exd and Hth, either antagonistic, as previously reported, or synergistic. This highlights context specific use of Exd/Hth, and a similar context specific use of Abd-B intrinsic protein requirements.
Hox蛋白是同源结构域(HD)转录因子家族的一个亚群,在发育和进化过程中为轴模式形成提供位置信息。Hox蛋白的功能特异性至少部分是通过与Pbc(果蝇中的额外齿状蛋白(Exd))和Meis/Prep(果蝇中的同胸蛋白(Hth))蛋白相互作用来实现的。我们目前对Hox蛋白特异性的大部分了解源于对前部和中部Hox蛋白的研究,确定了Hox/Pbc/Meis-Prep协同作用的分子和结构基础。后部Hox类蛋白,果蝇中的腹部B(Abd-B)和脊椎动物中的Hox9-13,相对较少被研究。它们与前部和中部类Hox蛋白有很大差异,HD序列保守程度低,且缺乏核心的典型Pbc相互作用基序。在这里,我们利用几种发育背景探索Abd-B的功能如何与Exd/Hth的功能相互作用,研究相互表达控制、功能依赖性和内在蛋白质需求。结果确定了交叉调节相互作用,这些相互作用设定了正常发育所需的相对表达和活性水平。它们还揭示了器官特异性需求以及与Exd和Hth的二元功能相互作用,这种相互作用要么如先前报道的那样是拮抗的,要么是协同的。这突出了Exd/Hth在特定背景下的使用,以及Abd-B内在蛋白质需求在类似特定背景下的使用。