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Review
. 2002 Feb;1(1):22-32.
doi: 10.1128/EC.01.1.22-32.2002.

Gcn4p, a master regulator of gene expression, is controlled at multiple levels by diverse signals of starvation and stress

Alan G Hinnebusch  1 , Krishnamurthy Natarajan
Affiliations
Review

Gcn4p, a master regulator of gene expression, is controlled at multiple levels by diverse signals of starvation and stress

Alan G Hinnebusch et al. Eukaryot Cell. 2002 Feb.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Summary of diverse regulatory mechanisms controlling Gcn4p expression or activity and the signals to which they respond. Activation is depicted with arrows; inhibition is depicted with bars. The environmental or physiological conditions regulating these responses are color coded according to the aspect of Gcn4p being regulated, including its expression at the level of translation, transcription, or degradation or its function as an activator. The role of Gcn2p in stimulating Gcn4p function in response to UV or glucose refeeding needs to be verified and thus is depicted with a broken line. Question marks indicate a lack of knowledge concerning the regulatory factors involved. X, hypothetical repressor of Gcn4p that is negatively regulated by the proteosome. See the text for details.
FIG. 2.
FIG. 2.
Hypothetical model for the stimulatory role of the GCN1-GCN20 complex in the activation of GCN2 by uncharged tRNA in the ribosomal A site. GCN1 is shown as a black ribbon containing near its center the EF3-like region. GCN20 is shown as a light grey rod, with the EF3-related ATP binding cassettes (ABCs) located toward the C terminus (term) and the N-terminal segment bound to the EF3-like region of GCN1. A GCN2 dimer is shown as a pair of medium grey ribbons with tRNA bound to the HisRS-like domains. Both GCN1-GCN20 and GCN2 have ribosome binding activities, which for GCN2 are conferred by its C-terminal domain. By analogy with the activation of E. coli RelA protein by uncharged tRNA, we propose that uncharged tRNA bound to the ribosomal A site and base paired with the cognate codon in mRNA is the activating ligand for GCN2. Based on their similarity to EF3, GCN1 and GCN20 may facilitate the binding of uncharged tRNA to the A site (arrow 1) or the transfer of tRNA from the A site to the HisRS-like domain in GCN2 (arrow 2). The physical association between GCN1-GCN20 and the N-terminal portion of GCN2 is consistent with the second mechanism. (Taken from reference .)
FIG. 3.
FIG. 3.
Schematic representation of functional categories of Gcn4p target genes. When Gcn4p is induced under conditions of histidine starvation, it elicits the transcriptional activation of at least 539 genes, designated Gcn4p targets (shown above Gcn4p in the activation group). These genes were induced ≥2-fold by 3-AT treatment in wild-type cells and showed a ≥2.0-fold higher level of expression in wild-type cells than in gcn4Δ cells (in the presence of 3-AT) or in GCN4c cells than in GCN4 cells (in the absence of 3-AT). The numbers of Gcn4p targets in different functional categories are indicated. Many genes were repressed by a factor of ≥2.0 in response to 3-AT treatment and were dependent on Gcn4p for maximal repression under these conditions (depicted below Gcn4p in the repression group). Prominent among the repressed genes are those encoding RPs or translation initiation factors.
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