A key transcription factor for eukaryotic initiation factor-2 alpha is strongly homologous to developmental transcription factors and may link metabolic genes to cellular growth and development.
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.
Laboratory of Molecular Hematology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
B J
BJ
Efiok
J A
JA
Chiorini
B
B
Safer
D000595:Amino Acid Sequence; D002454:Cell Differentiation; D002455:Cell Division; D003001:Cloning, Molecular; D016384:Consensus Sequence; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D010442:Peptide Chain Initiation, Translational; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; C088388:alpha-Pal transcription factor; C072372:P3A2 regulatory protein, Strongylocentrotus purpuratus