A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins

Abstract

SUMMARY The trace element zinc is required for proper functioning of a large number of proteins, including various enzymes. However, most zinc-containing proteins are transcription factors capable of binding DNA and are named zinc finger proteins. They form one of the largest families of transcriptional regulators and are categorized into various classes according to zinc-binding motifs. This review focuses on one class of zinc finger proteins called zinc cluster (or binuclear) proteins. Members of this family are exclusively fungal and possess the well-conserved motif CysX2CysX6CysX5-12CysX2CysX6-8Cys. The cysteine residues bind to two zinc atoms, which coordinate folding of the domain involved in DNA recognition. The first- and best-studied zinc cluster protein is Gal4p, a transcriptional activator of genes involved in the catabolism of galactose in the budding yeast Saccharomyces cerevisiae. Since the discovery of Gal4p, many other zinc cluster proteins have been characterized; they function in a wide range of processes, including primary and secondary metabolism and meiosis. Other roles include regulation of genes involved in the stress response as well as pleiotropic drug resistance, as demonstrated in budding yeast and in human fungal pathogens. With the number of characterized zinc cluster proteins growing rapidly, it is becoming more and more apparent that they are important regulators of fungal physiology.

Two Zinc-Cluster Transcription Factors Control Induction of Alternative Oxidase in Neurospora crassa

“…These proteins form an abundant class of transcription factors in fungi (Macpherson et al 2006), including N. crassa (Borkovich et al 2004). We also confirmed the position of predicted introns by sequencing an aod-5 cDNA produced by RT-PCR.…”

“…The AIM contains two directly repeated CGG triplets separated by 7 bp, both copies of which are required for induction. This motif structure is typical of sequence elements recognized by transcription factors of the zinccluster family (Macpherson et al 2006). Here we describe the identification of the N. crassa aod-2 and aod-5 gene products as zinc-cluster transcription factors that control the expression of the aod-1 gene via interaction with the AIM sequence.…”

A novel polyamide SL-A92 as a potential fungal resistance blocker: synthesis and bioactivities in Candida albicans

“…Four kinds of CDR genes in C albicans have been cloned [13,[40][41][42] , but only over-expression of CDR1 and CDR2 resulted in azole resistance [43] . Tac1p is the major transcription factor needed for the regulation of CDR1 and CDR2, and is characterized by a highly conserved Zn(II) 2 Cys 6 zinc finger motif formed by six cysteines that coordinate two zinc atoms within the DNAbinding domain [11,44,45] . Previous studies have demonstrated that the binding site of Tac1p lies in the drug-responsive element (DRE) and consists of a direct CGG repeat with four intervening nucleotides (CGGAA/TATCGG) [44] .…”

“…Recently, we have demonstrated that RTA2 is also involved in calcineurin-mediated drug resistance in C albicans [9,10] . Some transcription regulatory factors of these MDR genes have been identified, and many of them are zinc cluster proteins, such as Tac1p, Fcr1p and Upc2p [11] . Zinc cluster proteins form one of the largest families of transcriptional regulators in eukaryotes, displaying variable secondary structures and enormous functional diversity, and they can bind as homodimers to CGG triplets that are oriented in everted, inverted, or direct repeats [11] .…”

“…Some transcription regulatory factors of these MDR genes have been identified, and many of them are zinc cluster proteins, such as Tac1p, Fcr1p and Upc2p [11] . Zinc cluster proteins form one of the largest families of transcriptional regulators in eukaryotes, displaying variable secondary structures and enormous functional diversity, and they can bind as homodimers to CGG triplets that are oriented in everted, inverted, or direct repeats [11] . These transcription factors, as well as the transcription processes, represent potential targets against MDR.…”