Sterol Regulatory Element Binding Proteins in Fungi: Hypoxic Transcription Factors Linked to Pathogenesis

American Society for Microbiology - Tập 9 Số 3 - Trang 352-359 - 2010
Clara M. Bien1, Peter J. Espenshade1
1Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Tóm tắt

ABSTRACT Sterol regulatory element binding proteins (SREBPs) are membrane-bound transcription factors whose proteolytic activation is controlled by the cellular sterol concentration. Mammalian SREBPs are activated in cholesterol-depleted cells and serve to regulate cellular lipid homeostasis. Recent work demonstrates that SREBP is functionally conserved in fungi. While the ability to respond to sterols is conserved, fungal SREBPs are hypoxic transcription factors required for adaptation to a low-oxygen environment. In the fission yeast Schizosaccharomyces pombe , oxygen regulates the SREBP homolog Sre1 by independently controlling both its proteolytic activation and its degradation. SREBP is also required for adaptation to hypoxia in the human pathogens Cryptococcus neoformans and Aspergillus fumigatus . In these organisms, SREBP is required for virulence and resistance to antifungal drugs, making the SREBP pathway a potential target for antifungal therapy.

Từ khóa


Tài liệu tham khảo

10.1371/journal.ppat.1000612

10.1111/j.1365-2958.2009.06895.x

10.1016/S1097-2765(02)00591-9

10.1016/S0092-8674(00)80213-5

10.1194/jlr.R800054-JLR200

10.1016/j.cmet.2008.09.004

10.1111/j.1365-2958.2007.05676.x

10.1128/EC.00207-09

10.1371/journal.ppat.0030022

10.1099/jmm.0.46548-0

10.1242/jcs.02866

10.1146/annurev.genet.41.110306.130315

10.1016/j.cell.2005.12.022

10.1099/mic.0.2008/017475-0

10.1101/sqb.2002.67.491

10.1016/S0092-8674(00)81362-8

10.1074/jbc.270.49.29422

10.1074/jbc.M701326200

10.1016/j.cell.2005.01.012

Hughes B. T. Espenshade P. J. . 2008. Oxygen-regulated degradation of fission yeast SREBP by Ofd1, a prolyl hydroxylase family member. EMBO J.27:1491–1501.

10.1128/MCB.02448-05

10.1016/S0959-437X(02)00010-2

10.1046/j.1365-2958.2003.03368.x

10.1128/MCB.21.19.6418-6428.2001

10.1038/emboj.2008.271

10.1111/j.1365-2958.2007.05844.x

10.1517/14656566.9.6.927

10.1002/yea.320101010

10.1093/genetics/150.4.1443

10.1128/AAC.49.5.1745-1752.2005

10.1128/EC.00155-06

10.1038/nri2607

10.1016/S0969-2126(98)00067-7

10.1038/ng0295-202

10.1016/S0034-5687(99)00028-6

10.1073/pnas.0700899104

10.1016/j.molcel.2004.06.019

10.1074/jbc.274.40.28549

10.1111/j.1462-5822.2009.01325.x

10.1111/j.1749-6632.2009.05038.x

10.1016/S0014-5793(99)01654-3

10.1016/S0092-8674(01)00518-9

10.1016/j.jmb.2006.06.040

10.1038/nrn1408

10.1128/MCB.26.7.2817-2831.2006

10.1534/genetics.105.053025

10.1128/MCB.21.19.6395-6405.2001

10.1371/journal.ppat.1000200

10.1172/JCI25740