PDR3/YBL005W Summary Help

Standard Name PDR3 1
Systematic Name YBL005W
Alias AMY2 , TPE2
Feature Type ORF, Verified
Description Transcriptional activator of the pleiotropic drug resistance network; regulates expression of ATP-binding cassette (ABC) transporters through binding to cis-acting PDRE sites (PDR responsive elements); post-translationally up-regulated in cells lacking functional mitochondrial genome; involved in diauxic shift; relative distribution to nucleus increases upon DNA replication stress; APCC(Cdh1) substrate; PDR3 has a paralog, PDR1, that arose from the whole genome duplication (2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and see Summary Paragraph)
Name Description Pleiotropic Drug Resistance 1
Chromosomal Location
ChrII:217470 to 220400 | ORF Map | GBrowse
Gbrowse
Genetic position: -10 cM
Gene Ontology Annotations All PDR3 GO evidence and references
  View Computational GO annotations for PDR3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Targets 3 genes
Regulators 5 genes
Resources
Classical genetics
null
Large-scale survey
null
overexpression
unspecified
Resources
89 total interaction(s) for 72 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 3
  • Co-fractionation: 1
  • Co-purification: 1
  • Two-hybrid: 6

Genetic Interactions
  • Dosage Rescue: 3
  • Negative Genetic: 18
  • Phenotypic Enhancement: 29
  • Phenotypic Suppression: 5
  • Positive Genetic: 3
  • Synthetic Growth Defect: 13
  • Synthetic Lethality: 1
  • Synthetic Rescue: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 976
Molecular Weight (Da) 112,570
Isoelectric Point (pI) 6.55
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrII:217470 to 220400 | ORF Map | GBrowse
SGD ORF map
Genetic position: -10 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2931 217470..220400 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000101
SUMMARY PARAGRAPH for PDR3

PDR1 and PDR3 encode zinc finger transcription factors that are regulators of the pleiotropic drug response in S. cerevisiae. Pdr1p and Pdr3p are 36% identical in amino acid composition (3) and can form homodimers or heterodimers (12). Pdr1p and Pdr3p serve as both transcriptional activators and repressors by binding to pleiotropic drug response elements (PDREs) present in the promoters of target genes involved in multidrug resistance (reviewed in 13, 14, and 15). A key feature of the PDRE consensus sequence, 5'-TCCGCGGA-3', is the presence of CGG triplets in an everted repeat orientation (16) and both Pdr1p and Pdr3p constitutively occupy both perfect and degenerate PDREs (12). These two factors have overlapping but not identical sets of target genes and the individual effect on any given shared target gene can also differ (17, 18 and references therein). This variation in regulatory ability may be due either to differences in post-translational modification or heterodimer formation with other transcriptional factors such as Rdr1p and Stb5p (19, 20). Targets include the ABC transporters encoded by PDR5, PDR10, PDR15, SNQ2, and YOR1, the hexose transporter genes HXT9 and HXT11, and sphingolipid biosynthetic genes such as IPT1 (21, and reviewed in 15). Pdr3p also participates in other processes that do not involve Pdr1p, such as retrograde response signaling (22, 7), as well as regulating the DNA damage-inducible genes MAG1 and DDI1 (23).

Loss of either PDR1 or PDR3 results in differential drug tolerance, and loss of both pdr1 and pdr3 results in severe drug hypersensitivity. Single pdr1 null mutants are markedly decreased in their resistance to different drugs while the affect of a single pdr3 null mutation is less severe (3 and 24). Hyperactive mutants of Pdr1p and Pdr3p often lead to enhanced drug resistance due to an increase in drug transporters (reviewed in 13), but only about 10% of the roughly 200 genes containing a PDRE-like element in their promoters respond transcriptionally to the hyperactive forms of Pdr1p and Pdr3p, indicating that factors beyond the presence of a PDRE may be necessary for transcriptional activation by Pdr1p and Pdr3p (reviewed in 14).

Pdr3p positively autoregulates its own transcription through two PDREs present in the PDR3 promoter. These PDREs are also recognized and regulated by Pdr1p (25). PDR3 expression is also downregulated in the absence of cell growth brought on by glucose or nitrogen limitation or when cells approach stationary phase (26). In cells which have lost their mitochondrial genome (rho0 cells), PDR3 expression varies depending on both strain background and carbon source (7). Cell stress is another regulator of PDR3 transcription through the action of the heat shock transcription factor Hsf1p (27). The heat shock HSP70 protein Ssa1p is able to bind to Pdr3p and may post-translationally negatively regulate Pdr3p activity (28).

Last updated: 2007-09-28 Contact SGD

References cited on this page View Complete Literature Guide for PDR3
1) Subik J, et al.  (1986) Genetic mapping of nuclear mucidin resistance mutations in Saccharomyces cerevisiae. A new pdr locus on chromosome II. Curr Genet 10(9):665-70
2) Wolfger H, et al.  (1997) The yeast ATP binding cassette (ABC) protein genes PDR10 and PDR15 are novel targets for the Pdr1 and Pdr3 transcriptional regulators. FEBS Lett 418(3):269-74
3) Delaveau T, et al.  (1994) PDR3, a new yeast regulatory gene, is homologous to PDR1 and controls the multidrug resistance phenomenon. Mol Gen Genet 244(5):501-11
4) Balzi E and Goffeau A  (1995) Yeast multidrug resistance: the PDR network. J Bioenerg Biomembr 27(1):71-6
5) Kean LS, et al.  (1997) Plasma membrane translocation of fluorescent-labeled phosphatidylethanolamine is controlled by transcription regulators, PDR1 and PDR3. J Cell Biol 138(2):255-70
6) Zhang X and Moye-Rowley WS  (2001) Saccharomyces cerevisiae multidrug resistance gene expression inversely correlates with the status of the F(0) component of the mitochondrial ATPase. J Biol Chem 276(51):47844-52
7) Devaux F, et al.  (2002) Genome-wide studies on the nuclear PDR3-controlled response to mitochondrial dysfunction in yeast. FEBS Lett 515(1-3):25-8
8) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
9) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
10) Ostapenko D, et al.  (2012) Identification of anaphase promoting complex substrates in S. cerevisiae. PLoS One 7(9):e45895
11) Zampar GG, et al.  (2013) Temporal system-level organization of the switch from glycolytic to gluconeogenic operation in yeast. Mol Syst Biol 9():651
12) Mamnun YM, et al.  (2002) The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo- and heterodimers in vivo. Mol Microbiol 46(5):1429-40
13) MacPherson S, et al.  (2006) A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiol Mol Biol Rev 70(3):583-604
14) Moye-Rowley WS  (2003) Transcriptional control of multidrug resistance in the yeast Saccharomyces. Prog Nucleic Acid Res Mol Biol 73():251-79
15) Jungwirth H and Kuchler K  (2006) Yeast ABC transporters-- a tale of sex, stress, drugs and aging. FEBS Lett 580(4):1131-8
16) Hellauer K, et al.  (1996) A novel DNA binding motif for yeast zinc cluster proteins: the Leu3p and Pdr3p transcriptional activators recognize everted repeats. Mol Cell Biol 16(11):6096-102
17) DeRisi J, et al.  (2000) Genome microarray analysis of transcriptional activation in multidrug resistance yeast mutants. FEBS Lett 470(2):156-60
18) Sidorova M, et al.  (2007) Loss-of-function pdr3 mutations convert the Pdr3p transcription activator to a protein suppressing multidrug resistance in Saccharomyces cerevisiae. FEMS Yeast Res 7(2):254-64
19) Hellauer K, et al.  (2002) Zinc cluster protein Rdr1p is a transcriptional repressor of the PDR5 gene encoding a multidrug transporter. J Biol Chem 277(20):17671-6
20) Akache B, et al.  (2004) Complex interplay among regulators of drug resistance genes in Saccharomyces cerevisiae. J Biol Chem 279(27):27855-60
21) Hallstrom TC, et al.  (2001) Coordinate control of sphingolipid biosynthesis and multidrug resistance in Saccharomyces cerevisiae. J Biol Chem 276(26):23674-80
22) Panwar SL and Moye-Rowley WS  (2006) Long Chain Base Tolerance in Saccharomyces cerevisiae Is Induced by Retrograde Signals from the Mitochondria. J Biol Chem 281(10):6376-84
23) Zhu Y and Xiao W  (2004) Pdr3 is required for DNA damage induction of MAG1 and DDI1 via a bi-directional promoter element. Nucleic Acids Res 32(17):5066-75
24) Katzmann DJ, et al.  (1994) Transcriptional control of the yeast PDR5 gene by the PDR3 gene product. Mol Cell Biol 14(7):4653-61
25) Delahodde A, et al.  (1995) Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance. Mol Cell Biol 15(8):4043-51
26) Mamnun YM, et al.  (2004) Expression regulation of the yeast PDR5 ATP-binding cassette (ABC) transporter suggests a role in cellular detoxification during the exponential growth phase. FEBS Lett 559(1-3):111-7
27) Hahn JS, et al.  (2006) A stress regulatory network for co-ordinated activation of proteasome expression mediated by yeast heat shock transcription factor. Mol Microbiol 60(1):240-51
28) Shahi P, et al.  (2007) Negative transcriptional regulation of multidrug resistance gene expression by an Hsp70 protein. J Biol Chem 282(37):26822-31