Efiok B J, Chiorini J A, Safer B
Laboratory of Molecular Hematology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1994 Jul 22;269(29):18921-30.
In response to growth, metabolic, and other signals, eukaryotic cells regulate protein biosynthesis through post-translational mechanisms which target the alpha subunit of eukaryotic initiation factor-2 (eIF-2 alpha). Previous efforts to study transcriptional mechanisms underlying this regulation identified a novel transcription factor (alpha-Pal) for the eIF-2 alpha gene. To gain insights into the overall biological function of alpha-Pal, we cloned its cDNA. Sequence analysis of the encoded protein reveals that alpha-Pal is a putative bZIP transcription factor. Surprisingly, both the protein sequence and the DNA-recognition site (TGCGCATGCGCA) of this human protein are strongly homologous to those of two evolutionarily distant developmental transcription factors, P3A2 and ewg. Since P3A2 directs territory-specific transcription of muscle genes in sea urchin embryos, and ewg apparently directs transcription of flight muscle and neuronal genes in Drosophila embryos, it is likely that alpha-Pal directs similar gene transcription during human embryogenesis. In other studies, we also identified genes containing alpha-Pal-binding sequences as those involved in cellular proliferation, or the growth-responsive metabolic pathways, energy transduction, translation, and DNA replication/repair. Such data suggest that alpha-Pal also functions to modulate the transcription of metabolic genes required for cellular growth.
作为对生长、代谢及其他信号的响应，真核细胞通过针对真核起始因子2（eIF-2α）α亚基的翻译后机制来调节蛋白质生物合成。以往研究转录调控机制的工作鉴定出一种针对eIF-2α基因的新型转录因子（α-Pal）。为深入了解α-Pal的整体生物学功能，我们克隆了其cDNA。对编码蛋白的序列分析表明，α-Pal是一种假定的bZIP转录因子。令人惊讶的是，这种人类蛋白的蛋白序列和DNA识别位点（TGCGCATGCGCA）与两种在进化上距离遥远的发育转录因子P3A2和ewg的蛋白序列和DNA识别位点高度同源。由于P3A2指导海胆胚胎中肌肉基因的区域特异性转录，而ewg显然指导果蝇胚胎中飞行肌肉和神经元基因的转录，所以α-Pal很可能在人类胚胎发生过程中指导类似的基因转录。在其他研究中，我们还鉴定出含有α-Pal结合序列的基因是那些参与细胞增殖、生长响应性代谢途径、能量转导、翻译以及DNA复制/修复的基因。这些数据表明，α-Pal还具有调节细胞生长所需代谢基因转录的功能。
