Transmembrane protein 85 from both human (<i>TMEM85</i>) and yeast (<i>YGL231c</i>) inhibit hydrogen peroxide mediated cell death in yeast

Ring, Giselle; Khoury, Chamel; Solar, Aidan J.; Yang, Zhao; Mandato, Craig A.; Greenwood, Michael T.

doi:10.1016/j.febslet.2008.06.042

Cited by 23 publications

(17 citation statements)

References 25 publications

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“…Interestingly, the heatmap of functional effects (SNAP2) shows that the beta-strand interrupting the N-terminal disordered region and the transmembrane helices are highly sensitive to point mutations (Figure 1C). LocTree3 and metastudent predictions, respectively, agree at high reliability with the experimental subcellular localization of EMC4 in the ER membrane and its function in apoptosis (61,62) (Figure 1D and E). Additionally, metastudent identifies ‘protein folding in endoplasmic reticulum’ as biological function (Figure 1D; directed graph of predicted GO terms in Supplementary Figure S1, Supporting Online Material).…”

Section: Use Casesupporting

confidence: 71%

“…the importance of the disordered N-terminus, and the importance of the beta-strand that breaks it. May be this will provide more detail on the suggested involvement in protein folding and in apoptosis (Figure 1D (62)).…”

Section: Use Casementioning

confidence: 98%

“…EMC4 is a small alpha-helical transmembrane protein with 183 residues. It is relatively well annotated, localizes to the membrane of the ER and is implicated in apoptosis (61,62). …”

Section: Use Casementioning

confidence: 99%

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PredictProtein—an open resource for online prediction of protein structural and functional features

Yachdav

Kloppmann

Kaján

et al. 2014

Nucleic Acids Research

562

438

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PredictProtein is a meta-service for sequence analysis that has been predicting structural and functional features of proteins since 1992. Queried with a protein sequence it returns: multiple sequence alignments, predicted aspects of structure (secondary structure, solvent accessibility, transmembrane helices (TMSEG) and strands, coiled-coil regions, disulfide bonds and disordered regions) and function. The service incorporates analysis methods for the identification of functional regions (ConSurf), homology-based inference of Gene Ontology terms (metastudent), comprehensive subcellular localization prediction (LocTree3), protein–protein binding sites (ISIS2), protein–polynucleotide binding sites (SomeNA) and predictions of the effect of point mutations (non-synonymous SNPs) on protein function (SNAP2). Our goal has always been to develop a system optimized to meet the demands of experimentalists not highly experienced in bioinformatics. To this end, the PredictProtein results are presented as both text and a series of intuitive, interactive and visually appealing figures. The web server and sources are available at http://ppopen.rostlab.org.

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Section: Use Casesupporting

confidence: 71%

Section: Use Casementioning

confidence: 98%

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PredictProtein—an open resource for online prediction of protein structural and functional features

Yachdav

Kloppmann

Kaján

et al. 2014

Nucleic Acids Research

562

438

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“…Other proteins identified represent a challenge since they are clearly able to prevent PCD from a number of different stresses in yeast, but the mechanism by which they carry out this function remains unknown. This class of protein includes some with well-known functions such as Vacuolar Protein Sorting 24 (VPS24) and the small GTP binding protein Ran as well as proteins that are essentially functional orphans including TMEM85 and TMEM14 (Khoury et al, 2007; Ring et al, 2008; Woo et al, 2008, 2011). Other Bax suppressors identified include the dUTP hydrolyzing enzyme dUTPase and the ceramide utilizing enzyme sphingomyelin synthase (Yang et al, 2006; Williams et al, 2011).…”

Section: Humanized Yeastmentioning

confidence: 99%

Untangling the Roles of Anti-Apoptosis in Regulating Programmed Cell Death using Humanized Yeast Cells

Clapp¹,

Portt²,

Khoury³

et al. 2012

Front. Oncol.

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Genetically programmed cell death (PCD) mechanisms, including apoptosis, are important for the survival of metazoans since it allows, among things, the removal of damaged cells that interfere with normal function. Cell death due to PCD is observed in normal processes such as aging and in a number of pathophysiologies including hypoxia (common causes of heart attacks and strokes) and subsequent tissue reperfusion. Conversely, the loss of normal apoptotic responses is associated with the development of tumors. So far, limited success in preventing unwanted PCD has been reported with current therapeutic approaches despite the fact that inhibitors of key apoptotic inducers such as caspases have been developed. Alternative approaches have focused on mimicking anti-apoptotic processes observed in cells displaying increased resistance to apoptotic stimuli. Hormesis and pre-conditioning are commonly observed cellular strategies where sub-lethal levels of pro-apoptotic stimuli lead to increased resistance to higher or lethal levels of stress. Increased expression of anti-apoptotic sequences is a common mechanism mediating these protective effects. The relevance of the latter observation is exemplified by the observation that transgenic mice overexpressing anti-apoptotic genes show significant reductions in tissue damage following ischemia. Thus strategies aimed at increasing the levels of anti-apoptotic proteins, using gene therapy or cell penetrating recombinant proteins are being evaluated as novel therapeutics to decrease cell death following acute periods of cell death inducing stress. In spite of its functional and therapeutic importance, more is known regarding the processes involved in apoptosis than anti-apoptosis. The genetically tractable yeast Saccharomyces cerevisiae has emerged as an exceptional model to study multiple aspects of PCD including the mitochondrial mediated apoptosis observed in metazoans. To increase our knowledge of the process of anti-apoptosis, we screened a human heart cDNA expression library in yeast cells undergoing PCD due to the conditional expression of a mammalian pro-apoptotic Bax cDNA. Analysis of the multiple Bax suppressors identified revealed several previously known as well as a large number of clones representing potential novel anti-apoptotic sequences. The focus of this review is to report on recent achievements in the use of humanized yeast in genetic screens to identify novel stress-induced PCD suppressors, supporting the use of yeast as a unicellular model organism to elucidate anti-apoptotic and cell survival mechanisms.

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“…54 However, there was no known function for TMEM85 before being identified as an anti-apoptotic protein. 55 Thus the number and the diversity of clones identified as Bax suppressors further serve to highlight the complexity of the apoptotic responses to Bax in yeast, and the usefulness of Bax-expressing yeast as a tool to identify and characterize new anti-apoptotic sequences (Table 1).…”

Section: Figure 1 Schematic Representation Of the Effects Of Heterolomentioning

confidence: 99%

Expressing and functional analysis of mammalian apoptotic regulators in yeast

Greenwood

Ludovico

2009

Cell Death Differ

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The ease by which yeast can be manipulated in conjunction with their similarities to cells of more complex metazoans makes many yeast species, particularly Saccharomyces cerevisae, very attractive models for the study of conserved evolutionary processes that occur in eukaryotes. The ability to functionally express heterologous genes in these cells has allowed the development of countless new and elegant approaches leading to detailed structure-function analysis of numerous mammalian genes. Of these, the most informative have been the studies involving the analysis of regulators that have no direct or obvious sequence orthologue in yeast, including members of the Bcl-2 family of proteins, caspases and tumour suppressors. Here we review the field and provide evidence that these studies have served to further understand mammalian apoptosis.

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Transmembrane protein 85 from both human (TMEM85) and yeast (YGL231c) inhibit hydrogen peroxide mediated cell death in yeast

Cited by 23 publications

References 25 publications

PredictProtein—an open resource for online prediction of protein structural and functional features

PredictProtein—an open resource for online prediction of protein structural and functional features

Untangling the Roles of Anti-Apoptosis in Regulating Programmed Cell Death using Humanized Yeast Cells

Expressing and functional analysis of mammalian apoptotic regulators in yeast

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