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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

  • Lin, Meng Institute of Biochemistry, Christian Albrecht University, Kiel, Germany
  • Unden, Heike Institute of Biochemistry, Christian Albrecht University, Kiel, Germany
  • Jacquier, Nicolas Division of Biochemistry, University of Fribourg, Switzerland
  • Schneiter, Roger Division of Biochemistry, University of Fribourg, Switzerland
  • Just, Ursula Institute of Biochemistry, Christian Albrecht University, Kiel, Germany
  • Höfken, Thomas Institute of Biochemistry, Christian Albrecht University, Kiel, Germany
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    30.09.2009
Published in:
  • Molecular Biology of the Cell. - 2009, vol. 20, no. 22, p. 4826-4837
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology, life sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301354
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