Rtg3p, a basic helix-loop-helix/leucine zipper protein that functions in mitochondrial-induced changes in gene expression, contains independent activation domains
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Rtg3p and Rtg1p are basic helix-loop-helix/leucine zipper protein transcription factors in yeast that interact and bind to sites in an upstream activation sequence element in the 5'-flanking region of CIT2, a gene encoding a peroxisomal isoform of citrate synthase. These factors are required both for basal expression of CIT2 and its elevated expression in cells with dysfunctional mitochondria, such as in respiratory-deficient petite cells lacking mitochondrial DNA (rho degrees ). This elevated expression of CIT2 is called the retrograde response. Here we show that fusion constructs between the Gal4p DNA binding domain and Rtg3p transactivate the expression of a LacZ reporter gene under the control of a GAL1 promoter element. We have identified two activation domains in Rtg3p: a strong carboxyl-terminal domain from amino acids 375-486, and a weaker amino-terminal domain from amino acids 1-175; neither of these activation domains contain the bHLH/Zip motif. We have also identified a serine/threonine-rich domain of Rtg3p within amino acids 176-282 that is inhibitory to transactivation. In addition, the transcriptional activity of the Gal4-Rtg3p fusion proteins does not require either Rtg1p or Rtg2p; the latter is a protein containing an hsp70-like ATP binding domain that is also necessary for CIT2 expression. In contrast, transcriptional activation by Gal4-Rtg1p fusion proteins requires the Rtg1p basic helix-loop-helix/leucine zipper protein domain, as well as Rtg3p and Rtg2p. These data suggest that transcriptional activation by the Rtg1p-Rtg3p complex is largely the function of Rtg3p. Experiments are also presented suggesting that Rtg3p is limiting for gene expression in respiratory-competent (rho+) cells.
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Rtg3, but not Rtg1, has a functional independent transcription activation domain.
“This is consistent with the observation that Rtg3, but not Rtg1, has a functional independent transcription activation domain (Rothermel et al. 1997), and with our results demonstrating that in C. albicans nuclear localization of Rtg1 depends on Rtg3, but not vice versa.”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Rothermel et al. 1997
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684 · see citing works
Murre, C., Page-McCaw, P., & Baltimore, D. (1989) · Cell · doi:10.1016/0092-8674(89)90682-x · Cited by 2,713 · see citing works
The protein Id: A negative regulator of helix-loop-helix DNA binding proteins
Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L., & Weintraub, H. M. (1990) · Cell · doi:10.1016/0092-8674(90)90214-y · Cited by 2,202 · see citing works
Schiestl, R. H., & Gietz, R. D. (1989) · Current Genetics · doi:10.1007/bf00340712 · Cited by 2,143 · see citing works
Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.Preprint
Verma, I. M., Stevenson, J. K., Schwarz, E. M., Antwerp, D. V., & Miyamoto, S. (1995) · Genes & Development · doi:10.1101/gad.9.22.2723 · Cited by 1,696 · see citing works
A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae
Schmitt, M. E., Brown, T. A., & Trumpower, B. L. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.10.3091 · Cited by 1,344 · see citing works
Cloning of a Factor Required for Activity of the Ah (Dioxin) Receptor
Hoffman, E. C., Reyes, H., Chu, F., Sander, F. C., Conley, L. H., Brooks, B. A., & Hankinson, O. (1991) · Science · doi:10.1126/science.1852076 · Cited by 958 · see citing works
Sequence-Specific DNA Binding by the c-Myc Protein
Blackwell, T. K., Kretzner, L., Blackwood, E. M., Eisenman, R. N., & Weintraub, H. M. (1990) · Science · doi:10.1126/science.2251503 · Cited by 863 · see citing works
Lassar, A. B., Davis, R. L., Wright, W. E., Kadesch, T. R., Murre, C., Voronova, A., Baltimore, D., & Weintraub, H. M. (1991) · Cell · doi:10.1016/0092-8674(91)90620-e · Cited by 836 · see citing works
Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain
Ferré-D’Amaré, A. R., Prendergast, G. C., Ziff, E. B., & Burley, S. K. (1993) · Nature · doi:10.1038/363038a0 · Cited by 719 · see citing works
Mad: A heterodimeric partner for Max that antagonizes Myc transcriptional activity
Ayer, D. E., Kretzner, L., & Eisenman, R. N. (1993) · Cell · doi:10.1016/0092-8674(93)90661-9 · Cited by 697 · see citing works
Susek, R. E., Ausubel, F. M., & Chory, J. (1993) · Cell · doi:10.1016/0092-8674(93)90459-4 · Cited by 638 · see citing works
Schulze‐Osthoff, K., Beyaert, R., Vandevoorde, V., Haegeman, G., & Fiers, W. C. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05978.x · Cited by 577 · see citing works
Ebert, B. L., Firth, J. D., & Ratcliffe, P. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.49.29083 · Cited by 569 · see citing works
Metabolic Pathways in Peroxisomes and Glyoxysomes
Tolbert, N. E. (1981) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.50.070181.001025 · Cited by 557 · see citing works
Association of the Ah receptor with the 90-kDa heat shock protein.
Perdew, G. H. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68314-0 · Cited by 517 · see citing works
CROSSTALK BETWEEN NUCLEAR AND MITOCHONDRIAL GENOMES
Poyton, R. Ο., & McEwen, J. E. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.003023 · Cited by 499 · see citing works
Philip, C. M., Rould, M. A., Weintraub, H. M., & Pabo, C. O. (1994) · Cell · doi:10.1016/0092-8674(94)90159-7 · Cited by 461 · see citing works
Ellenberger, T., Fass, D., Arnaud, M., & Harrison, S. C. (1994) · Genes & Development · doi:10.1101/gad.8.8.970 · Cited by 445 · see citing works
Myc and Max proteins possess distinct transcriptional activities
Kretzner, L., Blackwood, E. M., & Eisenman, R. N. (1992) · Nature · doi:10.1038/359426a0 · Cited by 445 · see citing works
Craig, E. A., Weissman, J. S., & Horwich, A. L. (1994) · Cell · doi:10.1016/0092-8674(94)90416-2 · Cited by 426 · see citing works
Liao, X., & Butow, R. A. (1993) · Cell · doi:10.1016/0092-8674(93)90050-z · Cited by 419 · see citing works
Self-citationCellular interactions in development : a practical approach
Hartley, D. A. (1993) · Oxford University Press eBooks · Cited by 378 · see citing works
[9] Construction and use of gene fusions to lacZ (β-galactosidase) that are expressed in yeast
Rose, M. D., & Botstein, D. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)01012-5 · Cited by 341 · see citing works
The Mitochondrial Genotype Can Influence Nuclear Gene Expression in Yeast
Parikh, V. S., Morgan, M. M., Scott, R., Clements, L. S., & Butow, R. A. (1987) · Science · doi:10.1126/science.3027892 · Cited by 324 · see citing works
Self-citationProliferation of microbodies in Saccharomyces cerevisiae
Marten Veenhuis, A., Mateblowski, M., Kunau, W. H., & Harder, W. (1987) · Yeast · doi:10.1002/yea.320030204 · Cited by 305 · see citing works
Denis, M. G., Cuthill, S., Wikström, A., Poellinger, L., & Gustafsson, J. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)80566-7 · Cited by 234 · see citing works
Jia, Y., Rothermel, B., Thornton, J., & Butow, R. A. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1110 · Cited by 219 · see citing works
Self-citationLiao, X. S., Small, W. C., Srere, P. A., & Butow, R. A. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.1.38 · Cited by 218 · see citing works
Self-citationProbst, M. R., Reisz-Porszasz, S., Agbunag, R. V., Ong, M. S., & Hankinson, O. (1993) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13218-5 · Cited by 214 · see citing works
Wilhelmsson, A., Cuthill, S., Denis, M. G., Wikström, A., Gustafsson, J.-Å., & Poellinger, L. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb08081.x · Cited by 198 · see citing works
Whitelaw, M. L., Pongratz, I., Wilhelmsson, A., Gustafsson, J.-Å., & Poellinger, L. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.4.2504 · Cited by 191 · see citing works
Whitelaw, M. L., Gustafsson, J.-Α., & Poellinger, L. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8343 · Cited by 161 · see citing works
Chelstowska, A., & Butow, R. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.30.18141 · Cited by 135 · see citing works
Self-citationSequence-Specific Transcriptional Activation by Myc and Repression by Max
Amin, C. S., Wagner, A. J., & Hay, N. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.1.383-390.1993 · Cited by 134 · see citing works
Ellenberger, T. (1994) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(94)90054-x · Cited by 124 · see citing works
Citrate synthase encoded by the CIT2 gene of Saccharomyces cerevisiae is peroxisomal.
Lewin, A. S., Hines, V., & Small, G. M. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.4.1399 · Cited by 119 · see citing works
Comparative enzymology of β-oxidation
Kunau, W. H., BüHNE, S., de la Garza, M., Kionka, C., Mateblowski, M., SCHULTZ‐BORCHARD, U., & Thieringer, R. (1988) · Biochemical Society Transactions · doi:10.1042/bst0160418 · Cited by 119 · see citing works
Schwarz, J. J., Chakraborty, T., Martin, J. F., Zhou, J.-M., & Olson, E. N. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.1.266 · Cited by 110 · see citing works
Rosenkrantz, M. S., Alam, T., Kim, K., et al. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.12.4509-4515.1986 · Cited by 104 · see citing works
Skoneczny, M., Chełstowska, A., & Rytka, J. (1988) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1988.tb14097.x · Cited by 91 · see citing works
Poellinger, L., Göttlicher, M., & Gustafsson, J.-Α. (1992) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(92)90076-i · Cited by 82 · see citing works
The Basic Helix-Loop-Helix/PAS Factor Sim Is Associated with hsp90:
McGuire, J., Coumailleau, P., Whitelaw, M. L., Gustafsson, J.-Α., & Poellinger, L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.52.31353 · Cited by 75 · see citing works
Rothermel, B. A., Shyjan, A. W., Etheredge, J. L., & Butow, R. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.49.29476 · Cited by 56 · see citing works
Self-citationZhou, J., & Olson, E. N. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.9.6232 · Cited by 48 · see citing works
Koonin, E. V. (1994) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(94)90275-5 · Cited by 41 · see citing works
Kos, W., Kal, A. J., van Wilpe, S., & Tabak, H. F. (1995) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(95)00127-3 · Cited by 35 · see citing works
Shyjan, A. W., & Buttow, R. A. (1993) · Current Biology · doi:10.1016/0960-9822(93)90212-7 · Cited by 24 · see citing works
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- Authors
- Rothermel, B. A., Thornton, J. L., & Butow, R. A.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Butow, Ronald A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-08
- Volume
- 272
- Issue
- 32
- Pages
- 19801-19807
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2088673986
- Cited by
- 112
- References
- 49
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 3 · 2012: 6
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM22525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- retrograde response, mitochondrial dysfunction, citrate synthase, peroxisomes, transactivation domain, GAL4 fusion proteins, transcriptional activation, upstream activating sequence, Saccharomyces cerevisiae
- MeSH terms
- Antigens, Fungal, Binding Sites, Citrate (si)-Synthase, DNA-Binding Proteins, Fungal Proteins, Lac Operon, Microbodies, Mitochondria, Promoter Regions, Genetic, Saccharomyces cerevisiae, Transcription Factors, Transcriptional Activation, Gene Expression, Leucine Zippers, Genes, Reporter, Helix-Loop-Helix Motifs, Saccharomyces cerevisiae Proteins, Macromolecular Substances, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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