Increased nuclear envelope permeability and Pep4p-dependent degradation of nucleoporins during hydrogen peroxide-induced cell death

Mason, D. Adam; Shul'ga, N. I.; Undavai, Satyen; Ferrando‐May, Elisa; Rexach, Michael; Goldfarb, David S.

doi:10.1016/j.femsyr.2005.07.008

Cited by 51 publications

(54 citation statements)

References 49 publications

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“…It localizes predominantly to the vacuolar compartment, but translocation of this protease from the vacuole to the cytosol has been described. The active enzyme migrates from the vacuole in H 2 O 2 -triggered apoptotic cells (41). Translocation is associated with an increase in vacuolar permeability.…”

Section: Discussionmentioning

confidence: 99%

Identification of Pep4p as the Protease Responsible for Formation of the SAGA-related SLIK Protein Complex

Spedale

Mischerikow

Heck

et al. 2010

Journal of Biological Chemistry

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The Saccharomyces cerevisiae Spt-Ada-Gcn5 acetyltransferase (SAGA) protein complex is a coactivator for transcription by RNA polymerase II and has various activities, including acetylation and deubuiqitination of histones and recruitment of TATA-binding protein to promoters. The Spt7p subunit is subject to proteolytic cleavage at its C terminus resulting in removal of the Spt8p-binding domain and generation of the SAGA-related SALSA/SAGA-like (SLIK) protein complex. Here, we report identification of the protease responsible for this cleavage. Screening of a protease knock-out collection revealed PEP4 to be required for cleavage of Spt7p within SAGA in vitro. Endogenous formation of truncated Spt7p was abolished in cells lacking PEP4. Purified Pep4p but not catalytic dead mutant Pep4p or unrelated Prc1p protease specifically cleaved Spt7p within SAGA into SLIK-related Spt7p. Interestingly, SAGA lacking Spt8p was more sensitive to Pep4p-mediated truncation of Spt7p, suggesting that Spt8p counteracted its own release from SAGA. Strains mimicking constitutive SLIK formation showed increased resistance to rapamycin treatment, suggesting a role for SLIK in regulating cellular responses to nutrient stress.Transcription initiation by RNA polymerase II is a dynamic process that is regulated by the interplay of a large number of factors. The class of coactivators orchestrates preinitiation complex formation by recruiting nucleosome remodelers, basal transcription factors, and histone modifiers. The evolutionary highly conserved Spt-Ada-Gcn5 acetyltransferase (SAGA)

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Section: Discussionmentioning

confidence: 99%

Identification of Pep4p as the Protease Responsible for Formation of the SAGA-related SLIK Protein Complex

Spedale

Mischerikow

Heck

et al. 2010

Journal of Biological Chemistry

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“…The present study identified several genes associated with protein folding and stabilization that are upregulated during recovery after H 2 O 2 stress, and therefore, might be important for the selective import of oxidized proteins into the vacuole. However, it has recently been shown that cells treated with H 2 O 2 release Pep4p into the cytoplasm (Mason et al, 2005). It is therefore conceivable that oxidized proteins may be degraded by Pep4p in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae

et al. 2006

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The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae Turnover of damaged molecules is considered to play a key role in housekeeping of cells exposed to oxidative stress, and during the progress of ageing. In this work, global changes in the transcriptome were analysed during recovery of yeast cells after H 2 O 2 stress. Regarding induced genes, those associated with protein fate were the most significantly over-represented. In addition to genes encoding subunits of the 20S proteasome, genes related to vacuolar proteolysis (PEP4 and LAP4), protein sorting into the vacuole, and vacuolar fusion were found to be induced. The upregulation of PEP4 gene expression was associated with an increase in Pep4p activity. The induction of genes related to proteolysis was correlated with an increased protein turnover after H 2 O 2 -induced oxidation. Furthermore, protein degradation and the removal of oxidized proteins decreased in Pep4p-deficient cells. Pep4p activity also increased during chronological ageing, and cells lacking Pep4p displayed a shortened lifespan associated with higher levels of carbonylated proteins. PEP4 overexpression prevented the accumulation of oxidized proteins, but did not increase lifespan. These results indicate that Pep4p is important for protein turnover after oxidative damage; however, increased removal of oxidized proteins is not sufficient to enhance lifespan.

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“…In fact, Pep4p (the homolog of mammalian cathepsin-D) has been shown to migrate out of the vacuoles and degrade nucleoporins upon H 2 O 2 -induced cell death. 84 However, the associated form(s) of death remains to be accurately characterized.…”

Section: Proteins and Pathways Regulating Yeast Apoptosismentioning

confidence: 99%

Apoptosis in yeast: triggers, pathways, subroutines

et al. 2010

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A cell's decision to die is controlled by a sophisticated network whose deregulation contributes to the pathogenesis of multiple diseases including neoplastic and neurodegenerative disorders. The finding, more than a decade ago, that baker's yeast (Saccharomyces cerevisiae) can undergo apoptosis uncovered the possibility to investigate this mode of programmed cell death (PCD) in a model organism that combines both technical advantages and a eukaryotic 'cell room.' Since then, numerous exogenous and endogenous triggers have been found to induce yeast apoptosis and multiple yeast orthologs of crucial metazoan apoptotic regulators have been identified and characterized at the molecular level. Such apoptosis-relevant orthologs include proteases such as the yeast caspase as well as several mitochondrial and nuclear proteins that contribute to the execution of apoptosis in a caspase-independent manner. Additionally, physiological scenarios such as aging and failed mating have been discovered to trigger apoptosis in yeast, providing a teleological interpretation of PCD affecting a unicellular organism. Due to its methodological and logistic simplicity, yeast constitutes an ideal model organism that is efficiently helping to decipher the cell death regulatory network of higher organisms, including the switches between apoptotic, autophagic, and necrotic pathways of cellular catabolism. Here, we provide an overview of the current knowledge about the apoptotic subroutine of yeast PCD and its regulation.

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Increased nuclear envelope permeability and Pep4p-dependent degradation of nucleoporins during hydrogen peroxide-induced cell death

Cited by 51 publications

References 49 publications

Identification of Pep4p as the Protease Responsible for Formation of the SAGA-related SLIK Protein Complex

Identification of Pep4p as the Protease Responsible for Formation of the SAGA-related SLIK Protein Complex

The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae

Apoptosis in yeast: triggers, pathways, subroutines

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