Carotenuto Pietro, Marino Natascia, Bello Anna Maria, D'Angelo Anna, Di Porzio Umberto, Lombardi Daniela, Zollo Massimo
CEINGE, Biotecnologie Avanzate Scarl, Via Comunale Margherita 482, 80145, Naples, Italy.
J Bioenerg Biomembr. 2006 Aug;38(3-4):233-46. doi: 10.1007/s10863-006-9044-z. Epub 2006 Oct 11.
A genetic interaction between PRUNE and NM23/NDPK has been postulated in Drosophila melanogaster. Many have focused on Drosophila for the genetic combination between PRUNE "knock down" and AWD/NM23 fly mutants bearing the P97S mutation (K-pn, Killer of PRUNE mutation). We postulated a role for PRUNE-NM23 interactions in vertebrate development, demonstrating a physical interaction between the human PRUNE and NM23-H1 proteins, and partially characterizing their functional significance in cancer progression. Here, we present an initial analysis towards the functional characterization of the PRUNE-NM23 interaction during mammalian embryogenesis. Our working hypothesis is that PRUNE, NM23-H1 and their protein-protein interaction partners have important roles in mammalian brain development and adult brain function. Detailed expression analyses from early mouse brain development to adulthood show significant co-expression of these two genes during embryonic stages of brain development, especially focusing on the cortex, hippocampus, midbrain and cerebellum. We hypothesize that their abnormal expression results in an altered pathway of activation, influencing protein complex formation and its protein partner interactions in early embryogenesis. In the adult brain, their function appears concentrated towards their enzyme activities, wherein biochemical variations can result in brain dysfunction.
在黑腹果蝇中，已推测PRUNE与NM23/NDPK之间存在基因相互作用。许多研究聚焦于果蝇中PRUNE“敲低”与携带P97S突变（K-pn，PRUNE杀手突变）的AWD/NM23果蝇突变体之间的基因组合。我们推测PRUNE-NM23相互作用在脊椎动物发育中起作用，证明了人类PRUNE与NM23-H1蛋白之间存在物理相互作用，并部分表征了它们在癌症进展中的功能意义。在此，我们对哺乳动物胚胎发育过程中PRUNE-NM23相互作用的功能表征进行初步分析。我们的工作假设是，PRUNE、NM23-H1及其蛋白质-蛋白质相互作用伙伴在哺乳动物脑发育和成年脑功能中起重要作用。从小鼠脑发育早期到成年期的详细表达分析表明，这两个基因在脑发育的胚胎阶段有显著的共表达，尤其集中在皮质、海马体、中脑和小脑。我们假设它们的异常表达会导致激活途径改变，影响早期胚胎发育中的蛋白质复合物形成及其蛋白质伙伴相互作用。在成年脑中，它们的功能似乎集中在酶活性上，其中生化变化可能导致脑功能障碍。
