Transcription factors and ABC transporters: from pleiotropic drug resistance to cellular signaling in yeast

Abstract

Budding yeast S. cerevisiae survives in microenvironments utilizing networks of regulators and ATPbinding cassette (ABC) transporters to circumvent toxins and a variety of drugs. Our understanding of transcriptional regulation of ABC transporters in yeast is mainly derived from the study of multidrug resistance protein networks. Over the past two decades, this research has not only expanded the role of transcriptional regulators in pleiotropic drug resistance (PDR) but evolved to include the role that regulators play in cellular signaling and environmental adaptation. Inspection of the gene networks of the transcriptional regulators and characterization of the ABC transporters has clarified that they also contribute to environmental adaptation by controlling plasma-membrane composition, toxic-metal sequestration, and oxidative-stress adaptation. Additionally, ABC transporters and their regulators appear to be involved in cellular signaling for adaptation of S. cerevisiae populations to nutrient availability. In this review we summarize the current understanding of the S. cerevisiae transcriptional regulatory networks and highlight recent work in other notable fungal organisms, underlining the expansion of the study of these gene networks across the kingdom fungi.

The Negative Effect of Protein Phosphatase Z1 Deletion on the Oxidative Stress Tolerance of Candida albicans Is Synergistic with Betamethasone Exposure

“…It is noteworthy that CAP1 coding for one of the major regulators in oxidative stress defense, as well as ATM1 , YCF1/MLT1 , SNQ2 ABC transporters, MRD1 multidrug efflux pump and PDR16 phosphatidylinositol transfer protein [ 51 , 55 ], were induced after exposing the KO strain to MSB ( Figure 3 , Table S3 ). The ABC transporters and their transcriptional regulators are known to be essential for adaptation to environmental changes [ 55 ]. The SNQ2 and YCF1 transporter genes are among the primary targets of the Yap1 homolog Cap1 bZIP-type transcription factor and are rapidly expressed in response to oxidative stress [ 55 ].…”

“…The ABC transporters and their transcriptional regulators are known to be essential for adaptation to environmental changes [ 55 ]. The SNQ2 and YCF1 transporter genes are among the primary targets of the Yap1 homolog Cap1 bZIP-type transcription factor and are rapidly expressed in response to oxidative stress [ 55 ]. Ycf1 is a vacuolar ABC transporter, which probably transports glutathione S-conjugates into the vacuoles [ 55 , 56 ].…”

“…The SNQ2 and YCF1 transporter genes are among the primary targets of the Yap1 homolog Cap1 bZIP-type transcription factor and are rapidly expressed in response to oxidative stress [ 55 ]. Ycf1 is a vacuolar ABC transporter, which probably transports glutathione S-conjugates into the vacuoles [ 55 , 56 ]. Moreover, the phosphatidylinositol transfer protein Pdr16, may provide C. albicans cells with protection against MSB via sensing of stress-dependent changes in sterol biosynthesis and membrane lipid composition, and modulating the activity of enzymes involved in ergosterol biosynthesis [ 57 ].…”

Multidrug Resistance in Mammals and Fungi—From MDR to PDR: A Rocky Road from Atomic Structures to Transport Mechanisms

“…Fungal ABC proteins are also quite diverse and are implicated in many biological functions, contributing to pivotal cellular processes, including cellular detoxification and stress adaptation [ 214 , 248 , 249 ]. Owing to space constraints, we will limit our discussion to paradigm fungal PDR family members implicated in drug resistance phenomena, but refer the reader to numerous recent reviews discussing fungal ABC proteins at large [ 249 , 250 ]. Fungal ABC proteins of the PDR subfamily are the closest eukaryotic orthologues of human ABCG family exporters [ 245 , 251 ].…”

The incredible diversity of structures and functions of ABC transporters

“…Provided with such a flexible and powerful tool to make cellular membranes selective, it is perhaps not surprising that evolution has found many uses for ABC proteins. This diversity of biological contexts in which ABCs operate, and the broad roles they play in homeostasis, signaling, protection, and disease are the overarching themes of this special issue [1–4].…”