In response to growth, metabolic and other signals, eukaryotic cells regulate protein biosynthesis through post-translational mechanisms which target the alpha subunit of eIF-2 (eIF-2alpha). Previous efforts to study transcriptional mechanisms underlying this regulation identified a novel transcription factor (alpha-Pal) for the eIF-2alpha 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 basic-leucine zipper(bZIP) transcription factor which binds to target sequence as dimers. 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; sea Urchin's P3A2 and Drosophila's ewg. Since P3A2 directs territory- specific transcription of muscle genes during sea Urchin embryogenesis, and ewg apparently directs transcription of flight muscle and neuronal genes during Drosophila embryogenesis, it is likely that alpha-Pal directs similar gene transcription during human embryogenesis. In other studies, we identified potential target genes for alpha-Pal 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. Experiments using recombinant and native alpha-Pal suggest that phosphorylation and heterodimerization are putative mechanisms by which alpha-Pal regulates transcription of target genes in response to growth activation.
