Class II Pi3ks at the Intersection Between Signal Transduction and Membrane Trafficking
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AN INVESTIGATION of the ROLE of PAK6 in TUMORIGENESIS By
AN INVESTIGATION OF THE ROLE OF PAK6 IN TUMORIGENESIS by JoAnn Roberts A Thesis Submitted to the Faculty of The Charles E. Schmidt College of Medicine In Partial Fulfillment of the Requirements for the Degree of Master of Science Florida Atlantic University Boca Raton, Florida August 2012 ACKNOWLEDGMENTS This material is based upon work supported by the National Science Foundation under Grant No. DGE: 0638662. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. I would like to thank and acknowledge my thesis advisor, Dr. Michael Lu, for his support and guidance throughout the writing of this thesis and design of experiments in this manuscript. I would also like to thank my colleagues for assistance in various trouble-shooting circumstances. Last, but certainly not least, I would like to thank my family and friends for their support in the pursuit of my graduate studies. iii ABSTRACT Author: JoAnn Roberts Title: An Investigation of the Role of PAK6 in Tumorigenesis Institution: Florida Atlantic University Thesis Advisor: Dr. Michael Lu Degree: Master of Science Year: 2012 The function and role of PAK6, a serine/threonine kinase, in cancer progression has not yet been clearly identified. Several studies reveal that PAK6 may participate in key changes contributing to cancer progression such as cell survival, cell motility, and invasiveness. Based on the membrane localization of PAK6 in prostate and breast cancer cells, we speculated that PAK6 plays a role in cancer progression cells by localizing on the membrane and modifying proteins linked to motility and proliferation. -
PIK3C2G (NM 004570) Human Mutant ORF Clone Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RC402758 PIK3C2G (NM_004570) Human Mutant ORF Clone Product data: Product Type: Mutant ORF Clones Product Name: PIK3C2G (NM_004570) Human Mutant ORF Clone Mutation Description: P146L Affected Codon#: 146 Affected NT#: 437 Nucleotide Mutation: PIK3C2G Mutant (P146L), Myc-DDK-tagged ORF clone of Homo sapiens phosphoinositide-3- kinase, class 2, gamma polypeptide (PIK3C2G) as transfection-ready DNA Effect: Dibees, ype 2, ssoiion wih Symbol: PIK3C2G Synonyms: PI3K-C2-gamma; PI3K-C2GAMMA Vector: pCMV6-Entry (PS100001) Tag: Myc-DDK ACCN: NM_004570 ORF Size: 4335 bp ORF Nucleotide >RC402758 representing NM_004570 Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGGCATATTCTTGGCAAACGGATCCAAATCCTAATGAATCACACGAAAAGCAGTATGAACACCAAGAAT TTCTCTTTGTAAATCAACCCCATTCTTCTAGCCAAGTCAGTCTGGGTTTTGATCAGATAGTAGATGAGAT CAGTGGCAAAATTCCACACTACGAGAGTGAAATTGATGAAAACACCTTTTTTGTGCCCACTGCACCAAAA TGGGACTCAACAGGGCATTCATTAAATGAAGCACACCAAATATCCTTGAATGAATTCACTTCTAAAAGCC GTGAACTCTCCTGGCATCAAGTTAGCAAAGCACCAGCAATTGGTTTTAGTCCTTCTGTGTTACCAAAACC TCAAAATACGAATAAAGAATGCTCCTGGGGAAGCCCCATAGGAAAACATCATGGTGCTGATGATTCCAGA TTCAGTATTTTAGCTCTATCATTCACAAGTTTGGATAAAATTAATCTAGAGAAAGAATTAGAAAATGAAA ATCATAACTACCATATAGGATTTGAAAGTAGCATTCCTCCAACAAATTCATCCTTCTCAAGTGACTTCAT GCCGAAAGAAGAGAATAAAAGGAGTGGACATGTGAACATTGTGGAACCATCTTTGATGCTTTTGAAAGGC -
Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry
BASIC RESEARCH www.jasn.org Phosphoinositide 3-Kinase-C2a Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst Formation † Irene Franco,* Jean Piero Margaria,* Maria Chiara De Santis,* Andrea Ranghino, ‡ Daniel Monteyne, Marco Chiaravalli,§ Monika Pema,§ Carlo Cosimo Campa,* ‡| Edoardo Ratto,* Federico Gulluni,* David Perez-Morga, Stefan Somlo,¶ Giorgio R. Merlo,* Alessandra Boletta,§ and Emilio Hirsch* *Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy; †Renal Transplantation Center “A. Vercellone”, Division of Nephrology, Dialysis and Transplantation, Department of Medical Sciences, Città della Salute e della Scienza, Hospital and Research Center for Experimental Medicine (CeRMS) and Center for Molecular Biotechnology, University of Torino, Turin, Italy; ‡Laboratoire de Parasitologie Moléculaire, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles, Gosselies, Charleroi, Belgium; §Division of Genetics and Cell Biology, Dibit San Raffaele Scientific Institute, Milan, Italy; |Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles, Gosselies, Belgium; and ¶Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut. ABSTRACT Signaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2a (PI3K-C2a)inrenal tubule-derived inner medullary collecting duct 3 cells and show that PI3K-C2a resides at the recycling endo- some compartment in proximity to the primary cilium base. In this subcellular location, PI3K-C2a controlled the activation of Rab8, a key mediator of cargo protein targeting to the primary cilium. -
The DNA Methylation Landscape of Glioblastoma Disease Progression Shows Extensive Heterogeneity in Time and Space
bioRxiv preprint doi: https://doi.org/10.1101/173864; this version posted August 9, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space Johanna Klughammer1*, Barbara Kiesel2,3*, Thomas Roetzer3,4, Nikolaus Fortelny1, Amelie Kuchler1, Nathan C. Sheffield5, Paul Datlinger1, Nadine Peter3,4, Karl-Heinz Nenning6, Julia Furtner3,7, Martha Nowosielski8,9, Marco Augustin10, Mario Mischkulnig2,3, Thomas Ströbel3,4, Patrizia Moser11, Christian F. Freyschlag12, Jo- hannes Kerschbaumer12, Claudius Thomé12, Astrid E. Grams13, Günther Stockhammer8, Melitta Kitzwoegerer14, Stefan Oberndorfer15, Franz Marhold16, Serge Weis17, Johannes Trenkler18, Johanna Buchroithner19, Josef Pichler20, Johannes Haybaeck21,22, Stefanie Krassnig21, Kariem Madhy Ali23, Gord von Campe23, Franz Payer24, Camillo Sherif25, Julius Preiser26, Thomas Hauser27, Peter A. Winkler27, Waltraud Kleindienst28, Franz Würtz29, Tanisa Brandner-Kokalj29, Martin Stultschnig30, Stefan Schweiger31, Karin Dieckmann3,32, Matthias Preusser3,33, Georg Langs6, Bernhard Baumann10, Engelbert Knosp2,3, Georg Widhalm2,3, Christine Marosi3,33, Johannes A. Hainfellner3,4, Adelheid Woehrer3,4#§, Christoph Bock1,34,35# 1 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. 2 Department of Neurosurgery, Medical University of Vienna, Vienna, Austria. 3 Comprehensive Cancer Center, Central Nervous System Tumor Unit, Medical University of Vienna, Austria. 4 Institute of Neurology, Medical University of Vienna, Vienna, Austria. 5 Center for Public Health Genomics, University of Virginia, Charlottesville VA, USA. 6 Department of Biomedical Imaging and Image-guided Therapy, Computational Imaging Research Lab, Medical University of Vi- enna, Vienna, Austria. -
Mutations in PIK3C2A Cause Syndromic Short Stature
University of Groningen Mutations in PIK3C2A cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction Tiosano, Dov; Baris, Hagit N; Chen, Anlu; Hitzert, Marrit M; Schueler, Markus; Gulluni, Federico; Wiesener, Antje; Bergua, Antonio; Mory, Adi; Copeland, Brett Published in: PLoS genetics DOI: 10.1371/journal.pgen.1008088 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2019 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Tiosano, D., Baris, H. N., Chen, A., Hitzert, M. M., Schueler, M., Gulluni, F., ... Buchner, D. A. (2019). Mutations in PIK3C2A cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction. PLoS genetics, 15(4), [e1008088]. https://doi.org/10.1371/journal.pgen.1008088 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. -
Analysis of Inherited and Somatic Variants to Decipher Canine Complex Traits
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1454 Analysis of inherited and somatic variants to decipher canine complex traits KATE MEGQUIER ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-513-0310-9 UPPSALA urn:nbn:se:uu:diva-347165 2018 Dissertation presented at Uppsala University to be publicly examined in B:22, BMC, Husargatan 3, Uppsala, Monday, 21 May 2018 at 13:15 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in English. Faculty examiner: David Sargan (University of Cambridge). Abstract Megquier, K. 2018. Analysis of inherited and somatic variants to decipher canine complex traits. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1454. 67 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0310-9. This thesis presents several investigations of the dog as a model for complex diseases, focusing on cancers and the effect of genetic risk factors on clinical presentation. In Papers I and II, we performed genome-wide association studies (GWAS) to identify germline risk factors predisposing US golden retrievers to hemangiosarcoma (HSA) and B- cell lymphoma (BLSA). Paper I identified two loci predisposing to both HSA and BLSA, approximately 4 megabases (Mb) apart on chromosome 5. Carrying the risk haplotype at these loci was associated with separate changes in gene expression, both relating to T-cell activation and proliferation. Paper II followed up on the HSA GWAS by performing a meta-analysis with additional cases and controls. This confirmed three previously reported GWAS loci for HSA and revealed three new loci, the most significant on chromosome 18. -
Beyond Traditional Morphological Characterization of Lung
Cancers 2020 S1 of S15 Beyond Traditional Morphological Characterization of Lung Neuroendocrine Neoplasms: In Silico Study of Next-Generation Sequencing Mutations Analysis across the Four World Health Organization Defined Groups Giovanni Centonze, Davide Biganzoli, Natalie Prinzi, Sara Pusceddu, Alessandro Mangogna, Elena Tamborini, Federica Perrone, Adele Busico, Vincenzo Lagano, Laura Cattaneo, Gabriella Sozzi, Luca Roz, Elia Biganzoli and Massimo Milione Table S1. Genes Frequently mutated in Typical Carcinoids (TCs). Mutation Original Entrez Gene Gene Rate % eukaryotic translation initiation factor 1A X-linked [Source: HGNC 4.84 EIF1AX 1964 EIF1AX Symbol; Acc: HGNC: 3250] AT-rich interaction domain 1A [Source: HGNC Symbol;Acc: HGNC: 4.71 ARID1A 8289 ARID1A 11110] LDL receptor related protein 1B [Source: HGNC Symbol; Acc: 4.35 LRP1B 53353 LRP1B HGNC: 6693] 3.53 NF1 4763 NF1 neurofibromin 1 [Source: HGNC Symbol;Acc: HGNC: 7765] DS cell adhesion molecule like 1 [Source: HGNC Symbol; Acc: 2.90 DSCAML1 57453 DSCAML1 HGNC: 14656] 2.90 DST 667 DST dystonin [Source: HGNC Symbol;Acc: HGNC: 1090] FA complementation group D2 [Source: HGNC Symbol; Acc: 2.90 FANCD2 2177 FANCD2 HGNC: 3585] piccolo presynaptic cytomatrix protein [Source: HGNC Symbol; Acc: 2.90 PCLO 27445 PCLO HGNC: 13406] erb-b2 receptor tyrosine kinase 2 [Source: HGNC Symbol; Acc: 2.44 ERBB2 2064 ERBB2 HGNC: 3430] BRCA1 associated protein 1 [Source: HGNC Symbol; Acc: HGNC: 2.35 BAP1 8314 BAP1 950] capicua transcriptional repressor [Source: HGNC Symbol; Acc: 2.35 CIC 23152 CIC HGNC: -
TRIM24 As an Oncogene in the Mammary Gland
The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 5-2018 TRIM24 as an Oncogene in the Mammary Gland Aundrietta Duncan Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Cancer Biology Commons, Medicine and Health Sciences Commons, and the Other Genetics and Genomics Commons Recommended Citation Duncan, Aundrietta, "TRIM24 as an Oncogene in the Mammary Gland" (2018). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 845. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/845 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. TRIM24 AS AN ONCOGENE IN THE MAMMARY GLAND by Aundrietta DeVan Duncan, M.S. APPROVED: ______________________________ Michelle C. Barton, Ph.D. Advisory Professor ______________________________ Richard -
1 Mutations in PIK3C2A Cause Syndromic Short Stature, Skeletal
bioRxiv preprint doi: https://doi.org/10.1101/488411; this version posted December 7, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Mutations In PIK3C2A Cause Syndromic Short Stature, Skeletal Abnormalities, and Cataracts Associated With Ciliary Dysfunction Dov Tiosano,1,2,17 Hagit Baris Feldman,2,3,17 Anlu Chen,4,17 Marrit M. Hitzert,5,17 Markus Schueler,6,17 Federico Gulluni,7,17 Antje Wiesener,8 Antonio Bergua,9 Adi Mory,3 Brett Copeland,10 Joseph G. Gleeson,10,11 Patrick Rump,5 Hester van Meer,12 Deborah A. Sival,12 Volker Haucke,13 Josh Kriwinsky14, Karl X. Knaup,6 André Reis,8 Nadine N. Hauer,8 Emilio Hirsch,7 Ronald Roepman,15 Rolph Pfundt,15 Christian T. Thiel,8,18 Michael S. Wiesener,6,18 Mariam G. Aslanyan,15,18 and David A. Buchner4,14,16,18* 1Division of Pediatric Endocrinology, Ruth Children's Hospital, Rambam Medical Center, Haifa 30196, Israel. 2Rappaport Family Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 30196, Israel. 3The Genetics Institute, Rambam Health Care Campus, Haifa 3109601, Israel. 4Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA. 5Department of Genetics, University of Groningen, University Medical Center Groningen, PO Box 30001 9700 RB Groningen, The Netherlands. 6Department of Nephrology and Hypertension, Friedrich-Alexander University Erlangen- Nürnberg, Erlangen, Germany. 7Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126, Torino, Italy. -
Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification Of
Published OnlineFirst June 20, 2017; DOI: 10.1158/1078-0432.CCR-17-1183 Genomic alterations in fatal forms of non-anaplastic thyroid cancer: Identification of MED12 and RBM10 as novel thyroid cancer genes associated with tumor virulence Tihana Ibrahimpasic1,2,⃰ Bin Xu4 ⃰ ,Iñigo Landa1, Snjezana Dogan4 , Sumit Middha4, Venkatraman Seshan6 , Shyam Deraje1, Diane L Carlson5, Jocelyn Migliecci2, Jeffrey A. Knauf1, Brian Untch1, Michael F. Berger1,4, Luc Morris1,2, R. Michael Tuttle3, Timothy Chan1, James A. Fagin1,3, Ronald Ghossein4, Ian Ganly1,2 Human Oncology and Pathogenesis Program1, Department of Head and Neck Surgery2, Department of Medicine3, Department of Pathology4, Department of Pathology, Cleveland Clinic5, Department of Epidemiology and Biostatistics6, Memorial Sloan Kettering Cancer Center, New York, New York, USA. ⃰TI and BX contributed equally to this work Correspondence: Ian Ganly MD PhD Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center 1275 York Avenue, New York, NY, 10065 Email: [email protected] ; Tel: 212 639 6244 Fax: 212 396 5560 Ronald Ghossein MD 1 Downloaded from clincancerres.aacrjournals.org on September 27, 2021. © 2017 American Association for Cancer Research. Published OnlineFirst June 20, 2017; DOI: 10.1158/1078-0432.CCR-17-1183 Department of Pathology,Memorial Sloan Kettering Cancer Center 1275 York Avenue, New York, NY, 10065 Email: [email protected] Running Title: Genomics of fatal forms of non-anaplastic thyroid cancer Key words: Non-anaplastic, Thyroid cancer, Next-generation sequencing, MED12, RBM10. Word count: 4688 Conflicts of interest: The authors declare no potential conflicts of interestnone Financial support: This work was supported in part by NIH grant P30-CA008748 and the LesLois Family Foundation 2 Downloaded from clincancerres.aacrjournals.org on September 27, 2021. -
Genomic Analysis of Allele-Specific Expression in the Mouse Liver
bioRxiv preprint doi: https://doi.org/10.1101/024588; this version posted August 13, 2015. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 TITLE: Genomic analysis of allele-specific expression in the mouse liver Ashutosh K. Pandey* and Robert W. Williams* *Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, 38103 bioRxiv preprint doi: https://doi.org/10.1101/024588; this version posted August 13, 2015. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 2 RUNNING TITLE: Allele-specific expression in liver KEYWORDS: BXD, DBA/2J, haplotype-aware alignment, purifying selection, cis eQTL CORRESPONDING AUTHOR: Ashutosh K. Pandey 855 Monroe Avenue, Suite 512 Memphis, TN, 38163 Phone: 901-448-1761 Email addresses: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/024588; this version posted August 13, 2015. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 3 ABSTRACT Genetic differences in gene expression contribute significantly to phenotypic diversity and differences in disease susceptibility. In fact, the great majority of causal variants highlighted by genome-wide association are in non-coding regions that modulate expression. In order to quantify the extent of allelic differences in expression, we analyzed liver transcriptomes of isogenic F1 hybrid mice. Allele-specific expression (ASE) effects are pervasive and are detected in over 50% of assayed genes. -
(PX) Domains Based on Their Phosphoinositide Binding Specificities
ARTICLE https://doi.org/10.1038/s41467-019-09355-y OPEN Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities Mintu Chandra1, Yanni K.-Y. Chin1, Caroline Mas1,6, J. Ryan Feathers2, Blessy Paul1, Sanchari Datta2, Kai-En Chen 1, Xinying Jia 3, Zhe Yang4, Suzanne J. Norwood1, Biswaranjan Mohanty5, Andrea Bugarcic1, Rohan D. Teasdale1,4, W. Mike Henne2, Mehdi Mobli 3 & Brett M. Collins1 1234567890():,; Phox homology (PX) domains are membrane interacting domains that bind to phosphati- dylinositol phospholipids or phosphoinositides, markers of organelle identity in the endocytic system. Although many PX domains bind the canonical endosome-enriched lipid PtdIns3P, others interact with alternative phosphoinositides, and a precise understanding of how these specificities arise has remained elusive. Here we systematically screen all human PX domains for their phospholipid preferences using liposome binding assays, biolayer interferometry and isothermal titration calorimetry. These analyses define four distinct classes of human PX domains that either bind specifically to PtdIns3P, non-specifically to various di- and tri- phosphorylated phosphoinositides, bind both PtdIns3P and other phosphoinositides, or associate with none of the lipids tested. A comprehensive evaluation of PX domain structures reveals two distinct binding sites that explain these specificities, providing a basis for defining and predicting the functional membrane interactions of the entire PX domain protein family. 1 Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia. 2 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 3 Centre for Advanced Imaging and School of Chemistry and Molecular Biology, The University of Queensland, St.