Activity of the
            <i>Kluyveromyces lactis</i>
            Pdr5 Multidrug Transporter Is Modulated by the Sit4 Protein Phosphatase

Chen, Xin Jie

doi:10.1128/jb.183.13.3939-3948.2001

Cited by 21 publications

(21 citation statements)

References 62 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1a and Table 2). Although ScSIT4 shares 77% identity with KlSIT4 at the nucleotide level, the deletion of ScSIT4 conferred sensitivity rather than resistance to the drugs, which is in contrast to the observations reported for K. lactis (Chen et al , 2000; Chen, 2001). Compared with the wild‐type BY4741, the sit4 mutant strain in this background was hypersensitive to all the drugs tested.…”

Section: Resultscontrasting

confidence: 99%

The serine/threonine protein phosphatase Sit4p activates multidrug resistance in Saccharomyces cerevisiae

Miranda

Masuda

Ferreira‐Pereira

et al. 2010

FEMS Yeast Research

View full text Add to dashboard Cite

Multidrug resistance in Saccharomyces cerevisiae is frequently associated with gain-of-function mutations in zinc finger-containing transcription factors Pdr1p and Pdr3p. These regulatory proteins activate the expression of several ATP-binding cassette transporter genes, leading to elevated drug resistance. Here, we report that loss of the type 2A-related serine/threonine protein phosphatase Sit4p renders yeast cells sensitive to cycloheximide, azoles, daunorubicin and rhodamine 6G. This effect is a consequence of the decreased transcriptional levels of mainly PDR3 and its target genes, PDR5, SNQ2 and YOR1, which encode multidrug efflux pumps. The multidrug sensitivity of sit4 mutant cells is suppressed by the PDR1-3 mutant allele, which encodes a hyperactive form of Pdr1p. Sit4p is known to associate with regulatory proteins Sap155p, Sap4p, Sap185p and Sap190p. We found that the sap155 mutant strain is sensitive to azoles, but not to cycloheximide, while the sap155sap4 and sap185sap190 mutant strains are sensitive to both drugs. This finding indicates that the Sit4p-Sap protein complex subtly modulates the expression of drug efflux pumps. Drug resistance conferred by the expression of the Candida albicans CDR1 gene, an ortholog of PDR5 in S. cerevisiae, is also positively modulated by Sit4p. These data uncover a new regulatory pathway that connects multidrug resistance to Sit4p function.

show abstract

Section: Resultscontrasting

confidence: 99%

The serine/threonine protein phosphatase Sit4p activates multidrug resistance in Saccharomyces cerevisiae

Miranda

Masuda

Ferreira‐Pereira

et al. 2010

FEMS Yeast Research

View full text Add to dashboard Cite

show abstract

“…Phosphorylation of Ste6p, a protein required for yeast mating, appears to play a critical role in regulating protein localization and recycling [122,123]. The activity of Pdr5p is regulated by Sit4p-mediated phosphorylation [126]. Similarly, Ycf1p function is regulated by the yeast casein kinase 2 alpha protein, Cka1p [124].…”

Section: Regulation Of Non-mammalian Abc Transporters: a Brief Ovementioning

confidence: 99%

Regulation of ABC Transporter Function Via Phosphorylation by Protein Kinases

Stolarczyk¹,

Reiling²,

Paumi³

2011

CPB

View full text Add to dashboard Cite

ATP-binding cassette (ABC) transporters are multispanning membrane proteins that utilize ATP to move a broad range of substrates across cellular membranes. ABC transporters are involved in a number of human disorders and diseases [1]. Overexpression of a subset of the transporters has been closely linked to multidrug resistance in both bacteria and viruses and in cancer. A poorly understood and important aspect of ABC transporter biology is the role of phosphorylation as a mechanism to regulate transporter function. In this review, we summarize the current literature addressing the role of phosphorylation in regulating ABC transporter function. A comprehensive list of all the phosphorylation sites that have been identified for the human ABC transporters is presented, and we discuss the role of individual kinases in regulating transporter function. We address the potential pitfalls and difficulties associated with identifying phosphorylation sites and the corresponding kinase(s), and we discuss novel techniques that may circumvent these problems. We conclude by providing a brief perspective on studying ABC transporter phosphorylation.

show abstract

“…Our results support an effect of KlPDR16 on drug resistance. In K. lactis, the main efflux pump KlPdr5p is responsible for the extrusion of oligomycin from the cell (Chen, 2001). Interestingly, S. cerevisiae pdr16Δ mutant cells exhibit increased susceptibility neither to oligomycin nor to 4-nitroquinoline-N-oxide (van den Hazel et al, 1999).…”

Section: Saccharomyces Cerevisiae Cells Lacking Both Pdr16p Andmentioning

confidence: 99%

“…Interestingly, S. cerevisiae pdr16Δ mutant cells exhibit increased susceptibility neither to oligomycin nor to 4-nitroquinoline-N-oxide (van den Hazel et al, 1999). 3a), another known substrate of the KlPdr5p efflux pump (Kolaczkowski et al, 1996;Chen, 2001). In K. lactis, the main efflux pump KlPdr5p is responsible for the extrusion of oligomycin from the cell (Chen, 2001).…”

Section: Saccharomyces Cerevisiae Cells Lacking Both Pdr16p Andmentioning

confidence: 99%

Isolation and functional analysis of theKlPDR16gene

Goffa¹,

Balazfyova²,

Hervay³

et al. 2013

FEMS Yeast Res

View full text Add to dashboard Cite

The fight against multidrug-resistant pathogens requires an understanding of the underlying cellular mechanisms. In this work, we isolate and characterize one of the multidrug resistance determinants in Kluyveromyces lactis, the KlPDR16 gene. We show that KlPdr16p (345 aa), which belongs to the KlPdr1p regulon, is a functional homologue of the Saccharomyces cerevisiae Pdr16p. Deletion of KlPDR16 resulted in hypersensitivity of K. lactis cells to antifungal azoles, oligomycin, rhodamine 6G, 4-nitroquinoline-N-oxide and alkali metal cations. The Klpdr16∆ mutation led to a decreased content of ergosterol in whole-cell extract. In spite of the hypersensitivity of Klpdr16∆ mutant cells to rhodamine 6G and oligomycin, the transcript level of the KlPDR5 gene and the rhodamine 6G efflux in the mutant was the same as in the parental strain. Increased accumulation of rhodamine 6G in Klpdr16∆ cells indicates that KlPDR16 limits the rate of passive drug diffusion across the membrane, without affecting the glucose-induced drug export. The results obtained show that KlPDR16, similar to its orthologues in other yeast species, influences the passive drug diffusion into the yeast cell.

show abstract

Activity of the Kluyveromyces lactis Pdr5 Multidrug Transporter Is Modulated by the Sit4 Protein Phosphatase

Cited by 21 publications

References 62 publications

The serine/threonine protein phosphatase Sit4p activates multidrug resistance in Saccharomyces cerevisiae

The serine/threonine protein phosphatase Sit4p activates multidrug resistance in Saccharomyces cerevisiae

Regulation of ABC Transporter Function Via Phosphorylation by Protein Kinases

Isolation and functional analysis of theKlPDR16gene

Contact Info

Product

Resources

About