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Membrane Transport Inhibition as Mode of Action of Polyene Antimycotics: Recent Data Supported by Old Ones

Miroslava Opekarová1 and Widmar Tanner2*


1
Institute of Microbiology, Academy of Sciences of the Czech Republic, CZ-14220 Prague, Czech Republic

2Institute of Cell Biology and Plant Physiology, University of Regensburg, DE-93053 Regensburg, Germany

Article history:

Received March 29, 2013

Accepted September 23, 2013


Key words:

amphotericin B, nystatin, natamycin, sugar and amino acid transport

Summary:

Recent studies demonstrate that the actual interactions of polyenes with membrane
sterols are the basis for their antimycotic toxicity and not, as previously assumed, their potentialb to form pores. Therefore, sterols must play a vital role in membranes and this function is seriously disturbed once polyenes bind to and/or sequester them. Essential membrane proteins obviously require sterols for their activity. Among the various membrane protein/ergosterol interactions discussed herein, transport proteins of the plasma membrane are most likely the primary target for polyenes. All data available which support this notion are summarized in this review. Even data obtained almost 40 years ago could be useful in guiding future research.


*Corresponding author:        widmar.tanner@biologie.uni-regensburg.de

                                           

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The Yeast PHO Promoters as Paradigm for Transcriptional Regulation by Chromatin Remodelling: Current State of the Art

Slobodan Barbarić


Laboratory of Biochemistry, Faculty of Food Technology and Biotechnology,
University of Zagreb, HR-10000 Zagreb, Croatia

Article history
:
Received January 15, 2014
Accepted March 5, 2014

Key words:

chromatin remodelling, PHO genes, transcriptional regulation, Saccharomyces cerevisiae


Summary:

It has been widely acknowledged that modulation of chromatin structure at the promoter
region influences the usage of factor binding sites and thus provides first, important level of transcriptional regulation. Chromatin-remodelling complexes utilize the energy of ATP hydrolysis to disassemble nucleosomes, and their functions are prominently correlated with promoter activation and also repression. Mechanistic details of individual steps and their orchestration in complex remodelling events, as well as regulatory mechanisms controlling remodeller activity, are subjects of current and future studies. The yeast PHO5 promoter was the first and still is one of the best characterized examples of a massive chromatin transition associated with transcriptional activation. Studies with this promoter provided several breakthrough findings and established basic principles of chromatin-remodelling process. Recent studies have revealed a network of five remodellers from all four remodeller subfamilies involved in this chromatin transition. Importantly, requirement for chromatin remodellers at the PHO8 as well as at PHO84 promoter, activated by the same transactivator as PHO5, are rather different. All these findings point out that chromatin remodelling process is in general even more complex than presumed, and it could be expected that further studies with the well-established PHO promoter system will be rather valuable for its further understanding.

*Corresponding author:      sbarbari@pbf.hr                                         

                                         

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