The effects of transcription regulating genes

PDR1, pdr1-3 and PDR3 in pleiotropic drug resistance

Full-text article (461 kB)
(subscribers only)

Buy article on-line for £11.75
(get immediate access)

Eur. J. Mass Spectrom. 7, 195 - 205 (2001)

The effects of transcription regulating genes PDR1, pdr1-3 and PDR3 in pleiotropic drug resistance

Arkadiusz Nawrocki, Stephen J. Fey and Peter Mose Larsen^*
Centre for Proteome Analysis in Life Sciences, International Science Park Odense, University of Southern Denmark, Forskerparken 10B, 5230 Odense M, Denmark. E-mail:
André Goffeau
Chaire Internationale Blaise Pascal, Laboratoire Genetique Moleculaire, Ecole Normale Superieure, 46 rue dUlm, 75230 Paris Cedex 05, France
Peter Roepstorff
Department of Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark

ABSTRACT:

Mutations in the yeast PDR1 or PDR3 genes lead to acquisition of resistance towards various unrelated cytotoxic compounds. The broad range and different properties of these compounds indicate the existence of mechanisms which protect cellular targets, neutralise or expel the compounds from the cell. In wild type and pdr mutants, 83 proteins, out of 2706 detected by 2D gel electrophoresis, were differentially expressed. 53 of these could be identified by mass spectrometry. The functions of these 53 proteins fall into several metabolic groups demonstrating that drug-resistance phenotype is a mosaic response derived from such diverse functions as stress defence, endocytosis, oxidation and reduction, amino-acid synthesis and mitochondrial biogenesis. The patterns of synthesis of the selected proteins clearly demonstrates the complex interaction between Pdr1p and Pdr3p in exerting their regulatory functions. The data also indicate that, in the Saccharomyces cerevisiae pleiotropic drug resistance (PDR) phenomenon, translational events exert a more decisive effect than transcription in regulating the levels of active forms of the proteins involved.

Keywords: yeast, drug resistance, 2D gel electrophoresis, proteome analysis, image analysis

You can now buy this paper on-line in PDF format; it costs only £11.75. Just click on the BUY on-line button. You can pay on-line through a secure server and get access immediately.