Transcriptional regulation of E2F-1 and eIF-2 genes by alpha-pal: a potential mechanism for coordinated regulation of protein synthesis, growth, and the cell cycle.

alpha-Pal regulates the basal transcription of the alpha and beta subunits of eukaryotic initiation factor two (eIF-2), a rate-limiting enzyme for the initiation of protein biosynthesis. We recently showed that its global function may be to modulate the expression of key metabolic genes in response to cellular proliferation. In this paper, we examined a potential molecular mechanism by which alpha-Pal may achieve this function.

Interferon regulatory transcription factors are constitutively expressed and spatially regulated in the mouse lens.

Interferon regulatory factors (IRFs) are a family of transcription factors involved in regulation of cell growth and immunological responses. Nine IRFs have been described and they are expressed in a variety of cells, except for ICSBP and LSIRF/Pip, which are thought to be expressed exclusively in immune cells. Here, we show that IRF-1, IRF-2, ICSBP, and LSIRF/Pip are constitutively expressed in the mouse lens.

Interferon consensus sequence-binding protein is constitutively expressed and differentially regulated in the ocular lens.

Interferon signaling is mediated by STATs and interferon regulatory factor (IRF) families of transcription factors. Ten distinct IRFs have been described and most are expressed in a variety of cells except for interferon consensus sequence-binding protein (ICSBP) and lymphoid-specific IRF/Pip that are thought to be exclusively expressed in lymphoid cells. We show here for the first time that ICSBP is constitutively and inducibly expressed in the mouse lens.

Formation of alpha-Pal/Max heterodimers synergistically activates the eIF2-alpha promoter.

The transcription factor alpha-Pal recognizes two tandem palindromic repeats within the promoter of eukaryotic translation initiation factor 2-alpha (eIF2-alpha). Whereas both binding sites have the same "core domain" sequence (CGCATGCG), they differ with respect to their flanking sequences. Of the two sites, the 5'-cap proximal site has a higher binding affinity for alpha-Pal than does the 5'-cap distal site (Jacob, W.

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.