Nuclear localisation is crucial for the proapoptotic activity of the HtrA-like serine protease Nma111p

Walter, David; Henderson, Tracey A.; Yelton, Allison L.; O'Brien, Travis; Belanger, Kenneth D.; Geier, Susan J.; Fahrenkrog, Birthe

doi:10.1242/jcs.056887

Cited by 17 publications

(14 citation statements)

References 53 publications

(85 reference statements)

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“…Esp1 cleaves the cohesin Mcd1 in response to H 2 O 2 treatment (Yang et al 2008). Nma111, an ortholog of the human HtrA protease (Belanger et al 2009), cleaves Bir1, the yeast ortholog of the mammalian inhibitor of apoptosis factor (Walter et al 2006). Interestingly, these proteases exhibit full, partial, or no role in PCD execution depending on the stress (Liang et al 2008;Madeo et al 2009).…”

Section: Executioners Of the Programmed Cell Death Pathwaymentioning

confidence: 99%

Programmed Cell Death Initiation and Execution in Budding Yeast

Strich

2015

Genetics

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Apoptosis or programmed cell death (PCD) was initially described in metazoans as a genetically controlled process leading to intracellular breakdown and engulfment by a neighboring cell . This process was distinguished from other forms of cell death like necrosis by maintenance of plasma membrane integrity prior to engulfment and the well-defined genetic system controlling this process. Apoptosis was originally described as a mechanism to reshape tissues during development. Given this context, the assumption was made that this process would not be found in simpler eukaryotes such as budding yeast. Although basic components of the apoptotic pathway were identified in yeast, initial observations suggested that it was devoid of prosurvival and prodeath regulatory proteins identified in mammalian cells. However, as apoptosis became extensively linked to the elimination of damaged cells, key PCD regulatory proteins were identified in yeast that play similar roles in mammals. This review highlights recent discoveries that have permitted information regarding PCD regulation in yeast to now inform experiments in animals.

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Section: Executioners Of the Programmed Cell Death Pathwaymentioning

confidence: 99%

Programmed Cell Death Initiation and Execution in Budding Yeast

Strich

2015

Genetics

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“…For example, bacterial HtrA proteases are essential for the stress response to protein denaturation (58). In addition, HtrA functions as a nuclear serine protease essential for apoptosis in S. cerevisiae (59). Despite being widely characterized, phosphorylation-mediated activation has been reported only for mitochondrial HtrA2 (60).…”

Section: Hypothetical Proteinsmentioning

confidence: 99%

Temporal Dynamics of the Saccharopolyspora erythraea Phosphoproteome

Licona-Cassani

Lim

Marcellin

et al. 2014

Molecular & Cellular Proteomics

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Actinomycetes undergo a dramatic reorganization of metabolic and cellular machinery during a brief period of growth arrest ("metabolic switch") preceding mycelia differentiation and the onset of secondary metabolite biosynthesis. This study explores the role of phosphorylation in coordinating the metabolic switch in the industrial actinomycete Saccharopolyspora erythraea. A total of 109 phosphopeptides from 88 proteins were detected across a 150-h fermentation using open-profile two-dimensional LC-MS proteomics and TiO 2 enrichment. Quantitative analysis of the phosphopeptides and their unphosphorylated cognates was possible for 20 pairs that also displayed constant total protein expression. Enzymes from central carbon metabolism such as putative acetyl-coenzyme A carboxylase, isocitrate lyase, and 2-oxoglutarate dehydrogenase changed dramatically in the degree of phosphorylation during the stationary phase, suggesting metabolic rearrangement for the reutilization of substrates and the production of polyketide precursors. In addition, an enzyme involved in cellular response to environmental stress, trypsin-like serine protease (SACE_6340/NC_009142_6216), decreased in phosphorylation during the growth arrest stage. More important, enzymes related to the regulation of protein synthesis underwent rapid phosphorylation changes during this stage. Whereas the degree of phosphorylation of ribonuclease Rne/Rng (SACE_1406/NC_009142_1388) increased during the metabolic switch, that of two ribosomal proteins, S6 (SACE_7351/NC_009142_7233) and S32 (SACE_ 6101/NC_009142_5981), dramatically decreased during this stage of the fermentation, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Overall, we show the great potential of phosphoproteomic studies to explain microbial physiology and specifically provide evidence of dynamic protein phosphorylation events across the developmental cycle of actinomycetes. Molecular & Cellular

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“…H 2 O 2 treatment) and/or during chronological aging, a physiological cell death scenario in yeast. By employing a heterokaryon assay, Belanger et al [32] could show that Nma111p is not capable of shuttling between the nucleus and the cytoplasm and that it remains nuclear under steady-state conditions in the absence or presence of H 2 O 2 to induce apoptosis. The nuclear localization of Nma111p is due to a bipartite basic NLS (nuclear localization signal) within the first 35 amino acids of the protein (Figure 1).…”

Section: Nma111p Acts In the Cell Nucleusmentioning

confidence: 99%

“…The nuclear localization of Nma111p is due to a bipartite basic NLS (nuclear localization signal) within the first 35 amino acids of the protein (Figure 1). This NLS sequence is recognized by the nuclear import receptor Kap95p, which appears to be the major, but not exclusive, nuclear import receptor for Nma111p [32]. Importantly, disruption of any of the two stretches of the NLS affects the ability of Nma111p to promote cell death in response to oxidative stress and during chronological aging.…”

Section: Nma111p Acts In the Cell Nucleusmentioning

confidence: 99%

Nma111p, the pro-apoptotic HtrA-like nuclear serine protease in Saccharomyces cerevisiae: a short survey

Fahrenkrog

2011

Biochemical Society Transactions

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The baker's yeast, Saccharomyces cerevisiae, is also capable of undergoing programmed cell death or apoptosis, for example in response to viral infection as well as during chronological and replicative aging. Intrinsically, programmed cell death in yeast can be induced by, for example, H2O2, acetic acid or the mating-type pheromone. A number of evolutionarily conserved apoptosis-regulatory proteins have been identified in yeast, one of which is the HtrA (high-temperature requirement A)-like serine protease Nma111p (Nma is nuclear mediator of apoptosis). Nma111p is a nuclear serine protease of the HtrA family, which targets Bir1p, the only known inhibitor-of-apoptosis protein in yeast. Nma111p mediates apoptosis in a serine-protease-dependent manner and exhibits its activity exclusively in the nucleus. How the activity of Nma111p is regulated has remained largely elusive, but some evidence points to a control by phosphorylation. Current knowledge of Nma111p's function in apoptosis will be discussed in the present review.

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Nuclear localisation is crucial for the proapoptotic activity of the HtrA-like serine protease Nma111p

Cited by 17 publications

References 53 publications

Programmed Cell Death Initiation and Execution in Budding Yeast

Programmed Cell Death Initiation and Execution in Budding Yeast

Temporal Dynamics of the Saccharopolyspora erythraea Phosphoproteome

Nma111p, the pro-apoptotic HtrA-like nuclear serine protease in Saccharomyces cerevisiae: a short survey

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