Kusek J C, Greene R M, Pisano M M
Department of Molecular, Cellular and Craniofacial Biology, ULSD, University of Louisville, Birth Defects Center, Louisville, KY, USA.
Brain Res Bull. 2001 Jan 15;54(2):187-98. doi: 10.1016/s0361-9230(00)00447-0.
Development of the brain is determined by a strictly orchestrated program of proliferation, migration, apoptosis, differentiation, synaptogenesis, tract formation, and myelination. The E2F family of transcription factors, whose activity and functions are regulated in large part through interactions with the retinoblastoma (Rb) family of tumor suppressor proteins, has been implicated as a key regulator of proliferation, differentiation, and apoptosis in a variety of tissues. We have examined levels of the E2F and Rb families of proteins during both brain development and neural differentiation of P19 cells, and found the expression profiles during these two processes of neural development and maturation to be quite similar, i.e., strong up-regulation of p130, pronounced down-regulation of p107, moderate up-regulation of pRb, and significant down-regulation of most species of E2F and dimerization protein (DP). However, several specific isoforms, namely a 30 kDa form of DP-2, a 57 kDa species of E2F-3, a 59 kDa form of E2F-5 and the isoforms of E2F-1 recognized by the E2F-1 (KH-95) antibody were up-regulated suggesting that these particular isoforms of E2F and DP play a tissue-specific function in differentiation and maturation of nervous tissue. The potential role of the E2F/DP family of transcription factors in aspects of neural development and differentiation are considered.
大脑的发育由增殖、迁移、凋亡、分化、突触形成、神经束形成和髓鞘形成等严格编排的程序所决定。E2F转录因子家族的活性和功能在很大程度上通过与视网膜母细胞瘤（Rb）肿瘤抑制蛋白家族的相互作用来调节，该家族已被认为是多种组织中增殖、分化和凋亡的关键调节因子。我们检测了P19细胞脑发育和神经分化过程中E2F和Rb蛋白家族的水平，发现这两个神经发育和成熟过程中的表达谱非常相似，即p130强烈上调，p107明显下调，pRb适度上调，大多数E2F和二聚化蛋白（DP）种类显著下调。然而，几种特定的异构体，即30 kDa的DP-2形式、57 kDa的E2F-3种类、59 kDa的E2F-5形式以及被E2F-1（KH-95）抗体识别的E2F-1异构体上调，这表明E2F和DP的这些特定异构体在神经组织的分化和成熟中发挥组织特异性功能。本文探讨了E2F/DP转录因子家族在神经发育和分化方面的潜在作用。
