Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/8408
Title: The Cdc42 effectors Ste20, Cla4, and Skm1 down-regulate the expression of genes involved in sterol uptake by a mitogen-activated protein kinase-independent pathway
Authors: Unden, H
Jacquier, N
Schneiter, R
Just, U
Höfken, T
Keywords: Rho-type GTPase Cdc42;Ste20;Cla4;Skm1
Issue Date: 2009
Publisher: American Society for Cell Biology
Citation: Molecular Biology of the Cell, 20(22), 4826 - 4837, 2009
Abstract: In Saccharomyces cerevisiae, the Rho-type GTPase Cdc42 regulates polarized growth through its effectors, including the p21-activated kinases (PAKs) Ste20, Cla4, and Skm1. Previously, we demonstrated that Ste20 interacts with several proteins involved in sterol synthesis that are crucial for cell polarization. Under anaerobic conditions, sterols cannot be synthesized and need to be imported into cells. Here, we show that Ste20, Cla4, and Skm1 form a complex with Sut1, a transcriptional regulator that promotes sterol uptake. All three PAKs can translocate into the nucleus and down-regulate the expression of genes involved in sterol uptake, including the Sut1 targets AUS1 and DAN1 by a novel mechanism. Consistently, deletion of either STE20, CLA4, or SKM1 results in an increased sterol influx and PAK overexpression inhibits sterol uptake. For Ste20, we demonstrate that the down-regulation of gene expression requires nuclear localization and kinase activity of Ste20. Furthermore, the Ste20-mediated control of expression of sterol uptake genes depends on SUT1 but is independent of a mitogen-activated protein kinase signaling cascade. Together, these observations suggest that PAKs translocate into the nucleus, where they modulate expression of sterol uptake genes via Sut1, thereby controlling sterol homeostasis.
Description: © 2009 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0).
URI: http://www.molbiolcell.org/content/20/22/4826
http://bura.brunel.ac.uk/handle/2438/8408
DOI: http://dx.doi.org/10.1091/mbc.E09-01-0034
ISSN: 1059-1524
Appears in Collections:Biological Sciences
Publications
Dept of Life Sciences Research Papers

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