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.
Year: 1994
Type: article
Abstract: In response to growth, metabolic, and other signals, eukaryotic cells regulate protein biosynthesis through post-translational mechanisms which target the a subunit of eukaryotic initiation factor-2 (eIF-2a).Previous efforts to study transcriptional mechanisms underlying this regulation identified a novel transcription factor (a-Pal) for the eIF-2a gene.To gain insights into the overall biological function of a-Pal, we cloned its cDNA.Sequence analysis of the encoded protein reveals that a-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 a-Pal directs similar gene transcription during human embryogenesis.In other studies, we also identified genes containing a-Pal-binding sequences as those involved in cellular proliferation, or the growth-responsive metabolic pathways, energy transduction, translation, and DNA replicatiodrepair.Such data suggest that a-Pal also functions to modulate the transcription of metabolic genes required for cellular growth.Activation of protein biosynthesis is central to the expression of most genes.In eukaryotes, overall regulation of this process is dependent on the activity of eIF-2,' a heterotrimer consisting of a, p, and y subunits.eIF-2 catalyzes a rate-limiting step during translational initiation, that is, the binding of Met-tRNA to 40 S ribosomal subunits (Jagus et al., 1981, 1982; Safer and Jagus, 1981).The a subunit of eIF-2 (eIF-201) is a target for the regulation of protein synthesis in response to conditions such as growth activation, differentiation, metabolic changes, and viral infection (Cohen et al., 1990; Rosenwald et al., 1993; Duncan and Hershey, 1985a, 1985b;Katze et al., 1986;O'Malley et at., 1986).
Source: Journal of Biological Chemistry
Authors: B.J. Efiok, J.A. Chiorini, B. Safer
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1559737337