Genome-wide analysis of signaling networks regulating fatty acid-induced gene expression and organelle biogenesis

Institute for Systems Biology, Seattle, WA 98103, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 05/2008; 181(2):281-92. DOI: 10.1083/jcb.200710009
Source: PubMed


Reversible phosphorylation is the most common posttranslational modification used in the regulation of cellular processes. This study of phosphatases and kinases required for peroxisome biogenesis is the first genome-wide analysis of phosphorylation events controlling organelle biogenesis. We evaluate signaling molecule deletion strains of the yeast Saccharomyces cerevisiae for presence of a green fluorescent protein chimera of peroxisomal thiolase, formation of peroxisomes, and peroxisome functionality. We find that distinct signaling networks involving glucose-mediated gene repression, derepression, oleate-mediated induction, and peroxisome formation promote stages of the biogenesis pathway. Additionally, separate classes of signaling proteins are responsible for the regulation of peroxisome number and size. These signaling networks specify the requirements of early and late events of peroxisome biogenesis. Among the numerous signaling proteins involved, Pho85p is exceptional, with functional involvements in both gene expression and peroxisome formation. Our study represents the first global study of signaling networks regulating the biogenesis of an organelle.

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Available from: Fred David Mast, Oct 13, 2015
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    • " peroxisomes . Studies in H . polymorpha ( Opalinski et al . 2011 ) revealed that the in - sertion of the N - terminal amphipathic a - helix of Pex11 into the membrane causes the initial membrane curvature , which initiates organelle elongation . The activation of Pex11 in organelle fission may be regulated by phosphorylation / dephosphorylation ( Saleem et al . 2008 ; Knoblach and Rachubinski 2010 ) . Mutant studies indicate that strains pro - ducing constitutively dephosphorylated Pex11 show a phe - notype similar to pex11 cells , whereas strains expressing a phosphomimetic Pex11 mutant allele show enhanced per - oxisome proliferation , similar to cells overexpressing PEX11 ."
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    • "Rather, it was hypothesized that Snf1 regulates Adr1 via repression of another kinase or activation of a phosphatase, which controls Adr1 by phosphorylation/dephosphorylation at Ser230. To gain more insights into kinases/phosphatases modulating the peroxisomal oleate response, Saleem et al. (2008, 2010) recently performed two large-scale screens to unravel phosphorylation-based signaling networks: using 249 yeast kinase/ phosphatase deletion strains, the authors created a list of signaling pathways which positively and negatively influenced the peroxisomal response to oleate. In a second proteomic approach the authors directly screened for phosphorylated peptides enriched after growth on oleate (Saleem et al. 2010). "
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