Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control

Čopič, Alenka; Dorrington, Mariana; Pagant, Silvère; Barry, Justine; Lee, Marcus; Singh, Indira; Hartman, John L.; Miller, Elizabeth A.

doi:10.1534/genetics.109.101105

Cited by 66 publications

(49 citation statements)

References 58 publications

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“…the intra-ER chaperone Kar2 (a BiP homolog). The slow leak of Kar2 from the ER, through the Golgi and its secretion into the medium is a good way to observe dysregulated secretion (Copic et al, 2009). Indeed, overexpressing GFP-Pex35 (which led to a drastic increase in Arf1 levels) decreased secretion to 50% or less, similar to what is seen upon directly overexpressing Arf1 (Fig.…”

Section: Pex35 Modulates the Effect Of Arf1supporting

confidence: 54%

Pex35 is a regulator of peroxisome abundance

Yofe

Soliman

Chuartzman

et al. 2017

Journal of Cell Science

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Peroxisomes are cellular organelles with vital functions in lipid, amino acid and redox metabolism. The cellular formation and dynamics of peroxisomes are governed by PEX genes; however, the regulation of peroxisome abundance is still poorly understood. Here, we use a high-content microscopy screen in Saccharomyces cerevisiae to identify new regulators of peroxisome size and abundance. Our screen led to the identification of a previously uncharacterized gene, which we term PEX35, which affects peroxisome abundance. PEX35 encodes a peroxisomal membrane protein, a remote homolog to several curvature-generating human proteins. We systematically characterized the genetic and physical interactome as well as the metabolome of mutants in PEX35, and we found that Pex35 functionally interacts with the vesicle-budding-inducer Arf1. Our results highlight the functional interaction between peroxisomes and the secretory pathway.

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Section: Pex35 Modulates the Effect Of Arf1supporting

confidence: 54%

Pex35 is a regulator of peroxisome abundance

Yofe

Soliman

Chuartzman

et al. 2017

Journal of Cell Science

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“…Thus, cwc21D causes reduced levels of Erd2p and the additional loss of Erd1p may explain the growth defect. In support of this, another genome-wide screen showed that Cwc21p has a significant role in ER homeostasis; deletion of CWC21 causes unregulated ER to Golgi transport (Copic et al 2009). …”

Section: Cwc21 Interacts Genetically With Isy1mentioning

confidence: 94%

“…Expression of SRm300/SRRM2 also increases by 2.6-fold upon induction by calcium (Zagranichnaya et al 2005), suggesting a conserved mode of regulation. The link between Cwc21p, ERD2 pre-mRNA splicing, and ER homeostasis (Copic et al 2009) discussed above may be relevant to this.…”

Section: Cwc21p In the Regulation Of Splicingmentioning

confidence: 97%

Physical and genetic interactions of yeast Cwc21p, an ortholog of human SRm300/SRRM2, suggest a role at the catalytic center of the spliceosome

Grainger¹,

Barrass²,

Jacquier³

et al. 2009

RNA

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In Saccharomyces cerevisiae, Cwc21p is a protein of unknown function that is associated with the NineTeen Complex (NTC), a group of proteins involved in activating the spliceosome to promote the pre-mRNA splicing reaction. Here, we show that Cwc21p binds directly to two key splicing factors-namely, Prp8p and Snu114p-and becomes the first NTC-related protein known to dock directly to U5 snRNP proteins. Using a combination of proteomic techniques we show that the N-terminus of Prp8p contains an intramolecular fold that is a Snu114p and Cwc21p interacting domain (SCwid). Cwc21p also binds directly to the C-terminus of Snu114p. Complementary chemical cross-linking experiments reveal reciprocal protein footprints between the interacting Prp8 and Cwc21 proteins, identifying the conserved cwf21 domain in Cwc21p as a Prp8p binding site. Genetic and functional interactions between Cwc21p and Isy1p indicate that they have related functions at or prior to the first catalytic step of splicing, and suggest that Cwc21p functions at the catalytic center of the spliceosome, possibly in response to environmental or metabolic changes. We demonstrate that SRm300, the only SR-related protein known to be at the core of human catalytic spliceosomes, is a functional ortholog of Cwc21p, also interacting directly with Prp8p and Snu114p. Thus, the function of Cwc21p is likely conserved from yeast to humans.

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“…However, htz1D mutants have pleiotropic phenotypes: they grow poorly and are temperature sensitive , have membrane and ER defects (Lockshon et al 2007;Copic et al 2009), and show synthetic sickness/lethality with a very wide range of other chromatin-related mutants (Collins et al 2007). Two recent studies have cast doubts on whether the effects observed in htz1D mutants in S. cerevisiae are caused by loss of H2A.Z or by the "frustrated" activity of the Swr1 complex in the absence of H2A.Z (Halley et al 2010;Morillo-Huesca et al 2010a).…”

Section: Roles For H2az In Transcriptionmentioning

confidence: 99%

Chromatin and Transcription in Yeast

2012

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Understanding the mechanisms by which chromatin structure controls eukaryotic transcription has been an intense area of investigation for the past 25 years. Many of the key discoveries that created the foundation for this field came from studies of Saccharomyces cerevisiae, including the discovery of the role of chromatin in transcriptional silencing, as well as the discovery of chromatin-remodeling factors and histone modification activities. Since that time, studies in yeast have continued to contribute in leading ways. This review article summarizes the large body of yeast studies in this field.

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Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control

Cited by 66 publications

References 58 publications

Pex35 is a regulator of peroxisome abundance

Pex35 is a regulator of peroxisome abundance

Physical and genetic interactions of yeast Cwc21p, an ortholog of human SRm300/SRRM2, suggest a role at the catalytic center of the spliceosome

Chromatin and Transcription in Yeast

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