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, 2002 Dec.
Article
in En
| MEDLINE
| ID: mdl-12453227
ABSTRACT
The transcription factors Pdr1p and Pdr3p from Saccharomyces cerevisiae mediate pleiotropic drug resistance (PDR) by controlling expression of ATP-binding cassette (ABC) transporters such as Pdr5p, Snq2p and Yor1p. Previous in vitro studies demonstrated that Pdr1p and Pdr3p recognize so-called pleiotropic drug resistance elements (PDREs) in the promoters of target genes. In this study, we show that both Pdr1p and Pdr3p are phosphoproteins; Pdr3p isoforms migrate as two bands in gel electrophoresis, reflecting two distinct phosphorylation states. Most importantly, native co-immunoprecipitation experiments, using functional epitope-tagged Pdr1p/Pdr3p variants, demonstrate that Pdr1p and Pdr3p can form both homo- and heterodimers in vivo. Furthermore, in vivo footprinting of PDRE-containing promoters demonstrate that Pdr1p/Pdr3p constitutively occupy both perfect and degenerate PDREs in vivo. Thus, in addition to interaction with other regulators, differential dimerization provides a plausible explanation for the observation that Pdr3p and Pdr1p can both positively and negatively control PDR promoters with different combinations of perfect and degenerate PDREs.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Saccharomyces cerevisiae
/
Transcription Factors
/
Gene Expression Regulation, Fungal
/
Trans-Activators
/
ATP-Binding Cassette Transporters
/
Drug Resistance, Multiple, Fungal
/
DNA-Binding Proteins
Language:
En
Journal:
Mol Microbiol
Journal subject:
BIOLOGIA MOLECULAR
/
MICROBIOLOGIA
Year:
2002
Document type:
Article
Affiliation country:
Austria