Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2002 Aug;26(3):223-38.
doi: 10.1111/j.1574-6976.2002.tb00612.x.

Transmitting the Signal of Excess Nitrogen in Saccharomyces Cerevisiae From the Tor Proteins to the GATA Factors: Connecting the Dots

Affiliations
Free PMC article
Review

Transmitting the Signal of Excess Nitrogen in Saccharomyces Cerevisiae From the Tor Proteins to the GATA Factors: Connecting the Dots

Terrance G Cooper. FEMS Microbiol Rev. .
Free PMC article

Abstract

Major advances have recently occurred in our understanding of GATA factor-mediated, nitrogen catabolite repression (NCR)-sensitive gene expression in Saccharomyces cerevisiae. Under nitrogen-rich conditions, the GATA family transcriptional activators, Gln3 and Gat1, form complexes with Ure2, and are localized to the cytoplasm, which decreases NCR-sensitive expression. Under nitrogen-limiting conditions, Gln3 and Gat1 are dephosphorylated, move from the cytoplasm to the nucleus, in wild-type but not rna1 and srp1 mutants, and increase expression of NCR-sensitive genes. 'Induction' of NCR-sensitive gene expression and dephosphorylation of Gln3 (and Ure2 in some laboratories) when cells are treated with rapamycin implicates the Tor1/2 signal transduction pathway in this regulation. Mks1 is posited to be a negative regulator of Ure2, positive regulator of retrograde gene expression and to be itself negatively regulated by Tap42. In addition to Tap42, phosphatases Sit4 and Pph3 are also argued by some to participate in the regulatory pathway. Although a treasure trove of information has recently become available, much remains unknown (and sometimes controversial) with respect to the precise biochemical functions and regulatory pathway connections of Tap42, Sit4, Pph3, Mks1 and Ure2, and how precisely Gln3 and Gat1 are prevented from entering the nucleus. The purpose of this review is to provide background information needed by students and investigators outside of the field to follow and evaluate the rapidly evolving literature in this exciting field.

Figures

Fig. 1
Fig. 1
A: Zinc-finger homologies among the S. cerevisiae GATA family proteins. Filled circles represent mammalian GAT1 residues that contact the DNA. B: DNA target of the GAT1 protein. Filled and open circles identify nucleotides in the major and minor grooves, respectively, that contact the protein. C: Diagrams of the DAL5 and DAL7 promoters. Arrows indicate GATA sequences. Filled and dotted boxes indicate functional Gln3- and Dal80-binding sites, respectively. Open boxes indicate GATA sequences that do not appear to function. UIS and GC boxes represent other UAS elements that are not pertinent to the present discussion. Taken from [–6].
Fig. 2
Fig. 2
Model of reciprocal regulation of GATA factor gene expression and GATA factor regulation of NCR-sensitive gene expression per se. Arrowheads and bars designate positive and negative regulation, respectively. Dashed areas designate weak regulation. Taken from [11].
Fig. 3
Fig. 3
NCR. Closed and open boxes designate the presence and absence of transport gene expression. Compounds surrounding the yeast cells are all poor nitrogen sources.
Fig. 4
Fig. 4
(Left) Small portions of four mini-array analysis membranes demonstrating expression characteristics of a typical NCR-sensitive gene, YHR029c, and another, ZRT1, which is regulated by Gln3, but is not NCR-sensitive or Dal80-regulated. (Right) Summary of genes in various functional categories whose expression is NCR-sensitive. Modified from [15].
Fig. 5
Fig. 5
A: Sequence upstream of CAN1. Northern blot analysis of CAN1 expression in wild-type (W.T.) and mutants containing altered GATA elements. Proline (PRO) or glutamine (GLN) were used as sole nitrogen sources. Data in the left panel derived from wild-type chromosomal CAN1, while those in the right panel derived from wild-type and mutant CAN1 genes carried on a CEN-based plasmid [29]. B: Intracellular distribution GFP–Gln3 and GFP–Gat1 in glutamine or proline grown cultures. C: Model explaining the results obtained in A and B. Arrows and bars indicate positive and negative regulation, respectively. Xs indicate processes that no longer occur under the nitrogen conditions depicted. Modified from [12,29].
Fig. 6
Fig. 6
Structure of rapamycin, the molecule with which it interacts, and the pathways which respond to its addition to cells. Arrows and bars indicate positive and negative regulation, respectively.
Fig. 7
Fig. 7
A: Northern blot analysis of Dal80 expression following addition of rapamycin to the medium. ACT1 is the loading standard. B: Model summarizing results of genomic experiments in which nitrogen was in excess (YPD), limiting or rapamycin was added to the medium. Bars and arrowheads indicate negative and positive regulation, respectively. Xs designate processes that no longer occur under the nitrogen or rapamycin conditions indicated.
Fig. 8
Fig. 8
Myc-Gln3 localization in cells grown in the presence (+) or absence (−) of rapamycin. Bars and arrowheads indicate negative and positive regulation, respectively. X designates a process that no longer occurs in the presence of excess nitrogen but in the absence of rapamycin.
Fig. 9
Fig. 9
Model describing molecular interactions associated with Gln3 movement between the cytoplasm and nucleus of the cell. Redrawn from [38].
Fig. 10
Fig. 10
Domain map of the Gln3 molecule. Taken from [45].
Fig. 11
Fig. 11
Intracellular distribution of wild-type (pKA36) and mutant GFP–Gln3 fragments. Taken from [45].
Fig. 12
Fig. 12
Model of the regulatory pathway by which rapamycin induces GATA factor-mediated transcription. Model most closely resembles that proposed by Hall [27].
Fig. 13
Fig. 13
Domain map of Tor1.
Fig. 14
Fig. 14
Model of the interactions of Tor, Tap42, and PP2A phosphatases. Redrawn from [47].
Fig. 15
Fig. 15
Model of the associations between Tor, Tap42, Pph21, Cdc55 and Tpd3. Pph21 and Pph22 interact similarly. Redrawn from [48].
Fig. 16
Fig. 16
Models summarizing the operation of TAP42. The left side of the figure derives from the model of Hall [27], and the right side from that of Broach [48].
Fig. 17
Fig. 17
Northern blot analyses of DAL5 expression in double mutants provided with proline (PRO) or glutamine (GLN) as sole nitrogen source. Nuclear exclusion of GFP–Gln3 fragment 1–487 lacking the Tor1-binding domain. Modified from [45,55].
Fig. 18
Fig. 18
A: Molecular events in which Mks1 is reported to participate. B: Response of Ure2 and Gln3 dephosphorylation in wild-type and tap42-11 mutant strains. C: Model of Mks1-mediated regulation proposed by Schreiber [53]. Redrawn from [53].

Similar articles

See all similar articles

Cited by 142 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback