HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 38, 36924-36933, September 19, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/38/36924    most recent M301829200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tate, J. J. Articles by Cooper, T. G. Search for Related Content PubMed PubMed Citation Articles by Tate, J. J. Articles by Cooper, T. G. Social Bookmarking                      What's this?

Tor1/2 Regulation of Retrograde Gene Expression in Saccharomyces cerevisiae Derives Indirectly as a Consequence of Alterations in Ammonia Metabolism^*

Jennifer J. Tate and Terrance G. Cooper 

From the Department of Molecular Sciences, University of Tennessee, Memphis, Tennessee 38163

Retrograde genes of Saccharomyces cerevisiae encode the enzymes needed to synthesize -ketoglutarate, required for ammonia assimilation, when mitochondria are damaged or non-functional because of glucose fermentation. Therefore, it is not surprising that a close association exists between control of the retrograde regulon and expression of nitrogen catabolic genes. Expression of these latter genes is nitrogen catabolite repression (NCR)-sensitive, i.e. expression is low with good nitrogen sources (e.g. glutamine) and high when only poor (e.g. proline) or limiting nitrogen sources are available. It has been reported recently that both NCR-sensitive and retrograde gene expression is negatively regulated by glutamine and induced by treating cells with the Tor1/2 inhibitor, rapamycin. These conclusions predict that NCR-sensitive and retrograde gene expression should respond in parallel to nitrogen sources, ranging from those that highly repress NCR-sensitive transcription to those that elicit minimal NCR. Because this prediction did not accommodate earlier observations that CIT2 (a retrograde gene) expression is higher in glutamine than proline containing medium, we investigated retrograde regulation further. We show that (i) retrograde gene expression correlates with intracellular ammonia and -ketoglutarate generated by a nitrogen source rather than the severity of NCR it elicits, and (ii) in addition to its known regulation by NCR, NAD-glutamate dehydrogenase (GDH2) gene expression is down-regulated by ammonia under conditions where NCR is minimal. Therefore, intracellular ammonia plays a pivotal dual role, regulating the interface of nitrogen and carbon metabolism at the level of ammonia assimilation and production. Our results also indicate the effects of rapamycin treatment on CIT2 transcription, and hence Tor1/2 regulation of retrograde gene expression occur indirectly as a consequence of alterations in ammonia and glutamate metabolism.

Received for publication, February 20, 2003 , and in revised form, July 7, 2003.

^* This work was supported by National Institutes of Health Grant GM-35642. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 901-448-6179; Fax: 901-448-8462; E-mail: tcooper{at}utmem.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. Georis, A. Feller, J. J. Tate, T. G. Cooper, and E. Dubois Nitrogen Catabolite Repression-Sensitive Transcription as a Readout of Tor Pathway Regulation: The Genetic Background, Reporter Gene and GATA Factor Assayed Determine the Outcomes Genetics, March 1, 2009; 181(3): 861 - 874. [Abstract] [Full Text] [PDF]

				J. J. Tate, I. Georis, A. Feller, E. Dubois, and T. G. Cooper Rapamycin-induced Gln3 Dephosphorylation Is Insufficient for Nuclear Localization: Sit4 AND PP2A PHOSPHATASES ARE REGULATED AND FUNCTION DIFFERENTLY J. Biol. Chem., January 23, 2009; 284(4): 2522 - 2534. [Abstract] [Full Text] [PDF]

				I. Georis, J. J. Tate, T. G. Cooper, and E. Dubois Tor Pathway Control of the Nitrogen-responsive DAL5 Gene Bifurcates at the Level of Gln3 and Gat1 Regulation in Saccharomyces cerevisiae J. Biol. Chem., April 4, 2008; 283(14): 8919 - 8929. [Abstract] [Full Text] [PDF]

				J. J. Tate, A. Feller, E. Dubois, and T. G. Cooper Saccharomyces cerevisiae Sit4 Phosphatase Is Active Irrespective of the Nitrogen Source Provided, and Gln3 Phosphorylation Levels Become Nitrogen Source-responsive in a sit4-deleted Strain J. Biol. Chem., December 8, 2006; 281(49): 37980 - 37992. [Abstract] [Full Text] [PDF]

				C. McBryde, J. M. Gardner, M. de Barros Lopes, and V. Jiranek Generation of Novel Wine Yeast Strains by Adaptive Evolution Am. J. Enol. Vitic., December 1, 2006; 57(4): 423 - 430. [Abstract] [Full Text] [PDF]

				J. J. Tate, R. Rai, and T. G. Cooper Ammonia-specific Regulation of Gln3 Localization in Saccharomyces cerevisiae by Protein Kinase Npr1 J. Biol. Chem., September 22, 2006; 281(38): 28460 - 28469. [Abstract] [Full Text] [PDF]

				R. Usaite, K. R. Patil, T. Grotkjaer, J. Nielsen, and B. Regenberg Global Transcriptional and Physiological Responses of Saccharomyces cerevisiae to Ammonium, L-Alanine, or L-Glutamine Limitation Appl. Envir. Microbiol., September 1, 2006; 72(9): 6194 - 6203. [Abstract] [Full Text] [PDF]

				S. Giannattasio, Z. Liu, J. Thornton, and R. A. Butow Retrograde Response to Mitochondrial Dysfunction Is Separable from TOR1/2 Regulation of Retrograde Gene Expression J. Biol. Chem., December 30, 2005; 280(52): 42528 - 42535. [Abstract] [Full Text] [PDF]

				J. J. Tate, R. Rai, and T. G. Cooper Methionine Sulfoximine Treatment and Carbon Starvation Elicit Snf1-independent Phosphorylation of the Transcription Activator Gln3 in Saccharomyces cerevisiae J. Biol. Chem., July 22, 2005; 280(29): 27195 - 27204. [Abstract] [Full Text] [PDF]

				I. Dilova, S. Aronova, J. C.-Y. Chen, and T. Powers Tor Signaling and Nutrient-based Signals Converge on Mks1p Phosphorylation to Regulate Expression of Rtg1p{middle dot}Rtg3p-dependent Target Genes J. Biol. Chem., November 5, 2004; 279(45): 46527 - 46535. [Abstract] [Full Text] [PDF]

				K. H. Cox, J. J. Tate, and T. G. Cooper Actin Cytoskeleton Is Required For Nuclear Accumulation of Gln3 in Response to Nitrogen Limitation but Not Rapamycin Treatment in Saccharomyces cerevisiae J. Biol. Chem., April 30, 2004; 279(18): 19294 - 19301. [Abstract] [Full Text] [PDF]

				K. H. Cox, A. Kulkarni, J. J. Tate, and T. G. Cooper Gln3 Phosphorylation and Intracellular Localization in Nutrient Limitation and Starvation Differ from Those Generated by Rapamycin Inhibition of Tor1/2 in Saccharomyces cerevisiae J. Biol. Chem., March 12, 2004; 279(11): 10270 - 10278. [Abstract] [Full Text] [PDF]