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https://www.readbyqxmd.com/read/29670108/down-regulation-of-a-pro-apoptotic-pathway-regulated-by-pcaf-ada3-in-early-stage-gastric-cancer
#1
Daniella Brasacchio, Rita A Busuttil, Tahereh Noori, Ricky W Johnstone, Alex Boussioutas, Joseph A Trapani
The loss of p300/CBP-associated protein (PCAF) expression is associated with poor clinical outcome in gastric cancer, and a potential bio-marker for invasive and aggressive tumors. However, the mechanism linking loss of PCAF to the onset of gastric cancer has not been identified. Given that PCAF and its binding partner transcriptional adaptor protein 3 (ADA3) were recently shown to regulate the intrinsic (mitochondrial) pathway to apoptosis via epigenetic regulation of phosphofurin acidic cluster sorting proteins 1 and 2 (PACS1, PACS2), we analyzed PCAF, ADA3, and PACS1/2 expression in 99 patient-matched surgical samples ranging from normal gastric mucosa, through pre-malignant chronic gastritis and intestinal metaplasia to stage I-III invasive cancers...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29656858/a-recurrent-de-novo-pacs2-heterozygous-missense-variant-causes-neonatal-onset-developmental-epileptic-encephalopathy-facial-dysmorphism-and-cerebellar-dysgenesis
#2
Heather E Olson, Nolwenn Jean-Marçais, Edward Yang, Delphine Heron, Katrina Tatton-Brown, Paul A van der Zwaag, Emilia K Bijlsma, Bryan L Krock, E Backer, Erik-Jan Kamsteeg, Margje Sinnema, Margot R F Reijnders, David Bearden, Amber Begtrup, Aida Telegrafi, Roelineke J Lunsing, Lydie Burglen, Gaetan Lesca, Megan T Cho, Lacey A Smith, Beth R Sheidley, Christelle Moufawad El Achkar, Phillip L Pearl, Annapurna Poduri, Cara M Skraban, Jennifer Tarpinian, Addie I Nesbitt, Dietje E Fransen van de Putte, Claudia A L Ruivenkamp, Patrick Rump, Nicolas Chatron, Isabelle Sabatier, Julitta De Bellescize, Laurent Guibaud, David A Sweetser, Jessica L Waxler, Klaas J Wierenga, Jean Donadieu, Vinodh Narayanan, Keri M Ramsey, Caroline Nava, Jean-Baptiste Rivière, Antonio Vitobello, Frédéric Tran Mau-Them, Christophe Philippe, Ange-Line Bruel, Yannis Duffourd, Laurel Thomas, Stefan H Lelieveld, Janneke Schuurs-Hoeijmakers, Han G Brunner, Boris Keren, Julien Thevenon, Laurence Faivre, Gary Thomas, Christel Thauvin-Robinet
Developmental and epileptic encephalopathies (DEEs) represent a large clinical and genetic heterogeneous group of neurodevelopmental diseases. The identification of pathogenic genetic variants in DEEs remains crucial for deciphering this complex group and for accurately caring for affected individuals (clinical diagnosis, genetic counseling, impacting medical, precision therapy, clinical trials, etc.). Whole-exome sequencing and intensive data sharing identified a recurrent de novo PACS2 heterozygous missense variant in 14 unrelated individuals...
April 10, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29312533/loss-of-pacs-2-delays-regeneration-in-dss-induced-colitis-but-does-not-affect-the-apc-min-model-of-colorectal-cancer
#3
Sarah L Dombernowsky, Jeanette Schwarz, Jacob Samsøe-Petersen, Reidar Albrechtsen, Kim B Jensen, Gary Thomas, Marie Kveiborg
PACS-2 is a multifunctional sorting protein that mediates cell homeostasis. We recently identified PACS-2 in a functional genome-wide siRNA screen for novel regulators of the metalloproteinase ADAM17, the main sheddase for ligands of the ErbB receptor family. Of note, we showed that Pacs2 -/- mice have significantly reduced EGFR activity and proliferative index in the intestinal epithelium. As EGFR signaling is highly mitogenic for intestinal epithelial stem cells, and plays essential roles in intestinal epithelial regeneration and tumor development, we have now examined the role of PACS-2 in these processes...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/26108729/the-sorting-protein-pacs-2-promotes-erbb-signalling-by-regulating-recycling-of-the-metalloproteinase-adam17
#4
Sarah Louise Dombernowsky, Jacob Samsøe-Petersen, Camilla Hansson Petersen, Rachael Instrell, Anne-Mette Bornhardt Hedegaard, Laurel Thomas, Katelyn Mae Atkins, Sylvain Auclair, Reidar Albrechtsen, Kasper Johansen Mygind, Camilla Fröhlich, Michael Howell, Peter Parker, Gary Thomas, Marie Kveiborg
The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth and tumour progression. However, mechanisms acutely controlling ADAM17 cell-surface availability to modulate the extent of ErbB ligand release are poorly understood. Here, through a functional genome-wide siRNA screen, we identify the sorting protein PACS-2 as a regulator of ADAM17 trafficking and ErbB signalling. PACS-2 loss reduces ADAM17 cell-surface levels and ADAM17-dependent ErbB ligand shedding, without apparent effects on related proteases...
June 25, 2015: Nature Communications
https://www.readbyqxmd.com/read/24646523/mir-499-protects-cardiomyocytes-from-h-2o-2-induced-apoptosis-via-its-effects-on-pdcd4-and-pacs2
#5
Jiaji Wang, Zhuqing Jia, Chenguang Zhang, Min Sun, Weiping Wang, Ping Chen, Kangtao Ma, Youyi Zhang, Xianhui Li, Chunyan Zhou
Background microRNAs (miRNAs) are a class of small, non-coding endogenous RNAs that post-transcriptionally regulate some protein-coding genes. miRNAs play an important role in many cardiac pathophysiological processes, including myocardial infarction, cardiac hypertrophy, and heart failure. miR-499, specifically expressed in skeletal muscle and cardiac cells, is differentially regulated and functions in heart development. However, the function of miR-499 in mature heart is poorly understood. Results We report that cardiac-abundant miR-499 could protect neonatal rat cardiomyocytes against H 2O 2-induced apoptosis...
2014: RNA Biology
https://www.readbyqxmd.com/read/24464226/a-functional-genomics-screen-identifies-pcaf-and-ada3-as-regulators-of-human-granzyme-b-mediated-apoptosis-and-bid-cleavage
#6
D Brasacchio, T Noori, C House, A J Brennan, K J Simpson, O Susanto, P I Bird, R W Johnstone, J A Trapani
The human lymphocyte toxins granzyme B (hGrzB) and perforin cooperatively induce apoptosis of virus-infected or transformed cells: perforin pores enable entry of the serine protease hGrzB into the cytosol, where it processes Bid to selectively activate the intrinsic apoptosis pathway. Truncated Bid (tBid) induces Bax/Bak-dependent mitochondrial outer membrane permeability and the release of cytochrome c and Smac/Diablo. To identify cellular proteins that regulate perforin/hGrzB-mediated Bid cleavage and subsequent apoptosis, we performed a gene-knockdown (KD) screen using a lentiviral pool of short hairpin RNAs embedded within a miR30 backbone (shRNAmiR)...
May 2014: Cell Death and Differentiation
https://www.readbyqxmd.com/read/22488736/a-child-with-an-inherited-0-31%C3%A2-mb-microdeletion-of-chromosome-14q32-33-further-delineation-of-a-critical-region-for-the-14q32-deletion-syndrome
#7
J Lloyd Holder, Timothy E Lotze, Carlos Bacino, Sau-Wai Cheung
Chromosome 14q32.3 deletions are uncommon, with most described patients harboring a ring chromosome 14. Only 15 deletions have been described not associated with ring formation or other complex chromosomal rearrangements. Here, we describe a child with the smallest deletion of chromosome 14q32.3 reported in the literature. This child's deletion encompasses at most 0.305 Mb and six genes including NUDT14, BRF1, BTBD6, PACS2, MTA1, and TEX22. He has similar clinical findings, including mild facial dysmorphisms and intellectual disability, as other individuals with much larger deletions of the terminus of the long arm of chromosome 14...
August 2012: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/21935417/pseudomonas-aeruginosa-aes-1-exhibits-increased-virulence-gene-expression-during-chronic-infection-of-cystic-fibrosis-lung
#8
Sharna Naughton, Dane Parker, Torsten Seemann, Torsten Thomas, Lynne Turnbull, Barbara Rose, Peter Bye, Stuart Cordwell, Cynthia Whitchurch, Jim Manos
Pseudomonas aeruginosa, the leading cause of morbidity and mortality in people with cystic fibrosis (CF), adapts for survival in the CF lung through both mutation and gene expression changes. Frequent clonal strains such as the Australian Epidemic Strain-1 (AES-1), have increased ability to establish infection in the CF lung and to superimpose and replace infrequent clonal strains. Little is known about the factors underpinning these properties. Analysis has been hampered by lack of expression array templates containing CF-strain specific genes...
2011: PloS One
https://www.readbyqxmd.com/read/17714478/in-silico-comparison-of-pklc102-like-genomic-islands-of-pseudomonas-aeruginosa
#9
COMPARATIVE STUDY
Dieco Würdemann, Burkhard Tümmler
The genomic island pKLC102 first detected in Pseudomonas aeruginosa clone C strains can cross species barriers and exhibits the highest mobilization rate of a genomic island known to date. Homologous genomic islands of 81-108 kb in size were identified in the completely sequenced P. aeruginosa strains PA7, PA14, 2192, C3719 and PACS2, but not in strains PAO1 and LES. All pKLC102-like genomic islands are integrated in chromosomal tRNA(Lys) genes and share a syntenic set of more than 70 homologous ORFs, part of which are related to DNA replication or mobility genes...
October 2007: FEMS Microbiology Letters
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