Regulation by heme of sterol uptake in saccharomyces cerevisiae

ABSTRACTSut1 is a transcriptional regulator of the Zn(II)2Cys6family in the budding yeastSaccharomyces cerevisiae. The only function that has been attributed to Sut1 is sterol uptake under anaerobic conditions. Here, we show that Sut1 is also expressed in the presence of oxygen, and we identify a novel function for Sut1.SUT1overexpression blocks filamentous growth, a response to nutrient limitation, in both haploid and diploid cells. This inhibition by Sut1 is independent of its function in sterol uptake. Sut1 downregulates the expression ofGAT2,HAP4,MGA1,MSN4,NCE102,PRR2,RHO3, andRHO5. Several of these Sut1 targets (GAT2,HAP4,MGA1,RHO3, andRHO5) are essential for filamentation in haploids and/or diploids. Furthermore, the expression of the Sut1 target genes, with the exception ofMGA1, is induced during filamentous growth. We also show thatSUT1expression is autoregulated and inhibited by Ste12, a key transcriptional regulator of filamentation. We propose that Sut1 partially represses the expression ofGAT2,HAP4,MGA1,MSN4,NCE102,PRR2,RHO3, andRHO5when nutrients are plentiful. Filamentation-inducing conditions relieve this repression by Sut1, and the increased expression of Sut1 targets triggers filamentous growth.

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Sterol uptake in the yeast, Saccharomyces cerevisiae

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism ◽

10.1016/0005-2760(83)90118-2 ◽

1983 ◽

Vol 752 (2) ◽

pp. 240-243 ◽

Cited By ~ 8

Author(s):

Laurel F. Salerno ◽

L.W. Parks

Keyword(s):

Saccharomyces Cerevisiae ◽

Yeast Saccharomyces Cerevisiae ◽

Sterol Uptake

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An assessment of the specificity of sterol uptake and esterification in Saccharomyces cerevisiae.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)43004-9 ◽

1981 ◽

Vol 256 (24) ◽

pp. 13048-13054 ◽

Cited By ~ 3

Author(s):

F.R. Taylor ◽

L.W. Parks

Keyword(s):

Saccharomyces Cerevisiae ◽

Sterol Uptake

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SUT1 is a putative Zn[II]2Cys6-transcription factor whose upregulation enhances both sterol uptake and synthesis in aerobically growing Saccharomyces cerevisiae cells

European Journal of Biochemistry ◽

10.1046/j.1432-1327.2001.02029.x ◽

2001 ◽

Vol 268 (6) ◽

pp. 1585-1595 ◽

Cited By ~ 41

Author(s):

Frédérique Ness ◽

Stéphane Bourot ◽

Matthieu Régnacq ◽

Roberto Spagnoli ◽

Thierry Bergès ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Transcription Factor ◽

Sterol Uptake

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Tritium Suicide Selection Identifies Proteins Involved in the Uptake and Intracellular Transport of Sterols in Saccharomyces cerevisiae

Eukaryotic Cell ◽

10.1128/ec.00135-08 ◽

2008 ◽

Vol 8 (2) ◽

pp. 161-169 ◽

Cited By ~ 24

Author(s):

David P. Sullivan ◽

Alexander Georgiev ◽

Anant K. Menon

Keyword(s):

Saccharomyces Cerevisiae ◽

Abc Transporters ◽

Intracellular Transport ◽

Cytoplasmic Protein ◽

Intracellular Accumulation ◽

Transport Pathway ◽

Sterol Transport ◽

Sterol Uptake ◽

Transposon Insertions

ABSTRACT Sterol transport between the plasma membrane (PM) and the endoplasmic reticulum (ER) occurs by a nonvesicular mechanism that is poorly understood. To identify proteins required for this process, we isolated Saccharomyces cerevisiae mutants with defects in sterol transport. We used Upc2-1 cells that have the ability to take up sterols under aerobic conditions and exploited the observation that intracellular accumulation of exogenously supplied [3H]cholesterol in the form of [3H]cholesteryl ester requires an intact PM-ER sterol transport pathway. Upc2-1 cells were mutagenized using a transposon library, incubated with [3H]cholesterol, and subjected to tritium suicide selection to isolate mutants with a decreased ability to accumulate [3H]cholesterol. Many of the mutants had defects in the expression and trafficking of Aus1 and Pdr11, PM-localized ABC transporters that are required for sterol uptake. Through characterization of one of the mutants, a new role was uncovered for the transcription factor Mot3 in controlling expression of Aus1 and Pdr11. A number of mutants had transposon insertions in the uncharacterized Ydr051c gene, which we now refer to as DET1 (decreased ergosterol transport). These mutants expressed Aus1 and Pdr11 normally but were severely defective in the ability to accumulate exogenously supplied cholesterol. The transport of newly synthesized sterols from the ER to the PM was also defective in det1Δ cells. These data indicate that the cytoplasmic protein encoded by DET1 is involved in intracellular sterol transport.

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