DOCSLIB.ORG

Association of the FBXO11 Gene with Chronic Otitis Media with Effusion and Recurrent Otitis Media the Minnesota COME/ROM Family Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Association of the FBXO11 Gene with Chronic Otitis Media with Effusion and Recurrent Otitis Media the Minnesota COME/ROM Family Study ORIGINAL ARTICLE Association of the FBXO11 Gene With Chronic Otitis Media With Effusion and Recurrent Otitis Media The Minnesota COME/ROM Family Study Fernando Segade, PhD; Kathleen A. Daly, PhD; Dax Allred, BA; Pamela J. Hicks, BA; Miranda Cox, MS; Mark Brown, MS; Rachel E. Hardisty-Hughes, PhD; Steve D. M. Brown, PhD; Stephen S. Rich, PhD; Donald W. Bowden, PhD Objective: The FBXO11 gene is the human homo- analysis. In univariate genetic analysis, 1 reference SNP logue of the gene mutated in the novel deaf mouse mu- (hereinafter rs) (rs2134056) showed nominal evidence tant jeff (Jf), a single gene model of otitis media. We have of association to COME/ROM (P=.02), and 2 SNPs ap- evaluated single nucleotide polymorphisms (SNPs) in the proached significance (rs2020911, P=.06; rs3136367, FBXO11 gene for association with chronic otitis media P=.09). In multivariable analyses, including known risk with effusion/recurrent otitis media (COME/ROM). factors for COME/ROM (sex, exposure to smoking, at- tending day care centers, no prior breastfeeding, and hav- Design: A total of 13 SNPs were genotyped across the ing allergies), the evidence of independent association 98.7 kilobases of genomic DNA encompassing FBXO11. was reduced for each SNP (eg, rs2134056, from P=.02 Data were analyzed for single SNP association using gen- to P=.08). In subsequent analyses using the Pedigree Dis- eralized estimating equations, and haplotypes were evalu- equilibrium Test, the association of FBXO11 SNP ated using Pedigree Disequilibrium Test methods. rs2134056 (P=.06) with COME/ROM was confirmed. In- corporating multiple SNPs in 2- and 3-locus SNP hap- Patients: The Minnesota COME/ROM Family Study, a lotypes, those haplotypes containing rs2134056 also ex- group of 142 families (619 subjects) with multiple af- hibited evidence of association of FBXO11 and COME/ fected individuals with COME/ROM. ROM (P values ranging from .03 to .10). Main Outcome Measures: Genetic association of Conclusion: We have observed evidence consistent with COME/ROM with polymorphisms in FBXO11. an association between polymorphisms in FBXO11, the human homologue of the Jeff mouse model gene, and Results: The FBXO11 SNPs are contained in a single link- COME/ROM. age disequilibrium haplotype block. Ten of the 13 SNPs were sufficiently polymorphic in the sample to permit Arch Otolaryngol Head Neck Surg. 2006;132:729-733 HRONIC OTITIS MEDIA WITH ducted a linkage study (the Minnesota Author Affiliations: effusion (COME) and re- COME/ROM Family Study13) that re- Departments of Internal current otitis media vealed evidence for linkage to COME and Medicine (Drs Segade and (ROM) are relatively com- ROM on chromosome 10q and suggestive Bowden), Public Heath Sciences mon conditions, affect- evidence for linkage on chromosome 19q. (Ms Cox, Mr Brown, and ing 10% to 30% of children, and the rates Several case-control studies have identi- Dr Rich), and Biochemistry C 1-4 (Mr Allred, Ms Hicks, and of occurrence seem to be increasing. fied relationships between candidate genes Dr Bowden), and Center for These conditions often result in hearing and COME/ROM, including HLA anti- 5 6,7 14,15 16,17 Human Genomics (Drs Segade loss and middle ear sequelae. Disease gen, cytokine genes, and genes in- and Bowden, Mr Allred, and rates are highest in the preschool years and volved in the ability to clear infectious Ms Hicks), Wake Forest decline as children get older.1 These con- agents implicated in OM.18,19 To date, how- University School of Medicine, ditions are often treated with tympanos- ever, few detailed molecular genetic analy- Winston-Salem, NC; tomy tubes to ventilate the middle ear; this ses of genetic associations between candi- Department of Otolaryngology is the most common surgical procedure per- date genes and COME/ROM have been and Otitis Media Research formed in children in an ambulatory set- reported. Center, University of Minnesota ting.8 Epidemiologic studies2,9,10 have shown The FBXO11 gene is an intriguing can- School of Medicine, Minneapolis, (Dr Daly); and that a family history of these conditions in- didate for association with COME/ROM. Medical Research Council, crease a child’s personal risk for COME/ The deaf mouse mutant jeff represents a 11,12 20 Mammalian Genetics Unit ROM, and twin studies have demon- single gene model of COME, character- (Drs Hardisty-Hughes and strated a high degree of heritability for ROM ized by the development of OM in patho- Brown), Harwell, England. and otitis media (OM) duration. We con- gen-free conditions in the absence of any (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 132, JULY 2006 WWW.ARCHOTO.COM 729 ©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 other inflammatory disease. Animals with the jeff gene this study. We chose SNPs to cover the entire FBXO11 ge- (hereinafter, Jeff animals) present with fluid and pus ac- nomic sequence, including the 5Ј promoter region, exons, in- cumulation in the middle ear cavity, with diffuse muco- trons, and the 3Ј-untranslated region, and included rs2020911, sal inflammation, disruption of the eustachian epithe- rs3136367, rs3136371, rs3771285, rs3732191, rs330787, lium, and reduction of the lumen owing to abnormal rs2651767, rs2134056, rs960106, rs2937345, rs874869, 20 rs4952896, and rs7582252 (where rs indicates 1 reference SNP). growths. The jeff mutation appears to be fully pen- Of these SNPs, rs7582252, rs2937345, and rs3136371 were not etrant and has been mapped to the distal region of mouse polymorphic and were not included in subsequent analyses. 20 chromosome 17. A missense mutation has been iden- We performed genotyping of the FBXO11 SNP polymor- tified in Fbxo11, a gene located on this region of mouse phisms by employing the MassARRAY SNP genotyping sys- chromosome 17 (R. E. Hardisty-Hughes and S. D. M. tem (Sequenom Inc, San Diego, Calif) using a standard pro- Brown, unpublished data, 2006). The human ortholog, tocol.23 Total genomic DNA was purified from whole blood FBXO11, is located on chromosome 2 and encodes a 141- samples obtained from the subjects using PUREGENE DNA iso- residue protein that belongs to the F-box family of genes. lation kit (Gentra Inc, Minneapolis, Minn). We quantitated DNA FBXO11 is characterized by the presence of a 50–amino using standardized fluorometric readings on a Hoefer DyNA acid sequence, the F-box, which functions in protein- Quant 200 fluorometer (Hoefer Pharmacia Biotech Inc, San Fran- 21 cisco, Calif). Each sample was diluted to a final concentration protein interactions. The FBXO11 gene therefore rep- of 5 ng/µL. resents a strong candidate gene for OM. This article ex- amines polymorphisms in the FBXO11 gene for association in the human disease pathway for COME/ROM. STATISTICAL GENETIC ANALYSES METHODS We examined each pedigree for evidence of an incorrect fam- ily relationship by using genome scan data and PREST soft- ware.24 For each of the SNPs genotyped in this study, mende- PARTICIPANTS lian inconsistencies in their genotype assignment were examined using PEDCHECK software.25 Any genotypes inconsistent with All families and individuals in this study were recruited to par- 13 mendelian inheritance (9 total [0.001%]) were converted to miss- ticipate in the genetic linkage study. Families who were excluded ing. Following pedigree and genotype correction, maximum- from the linkage study because they lacked an affected sibling pair likelihood estimates of allele frequencies were computed us- with sufficient DNA were evaluated in this study. Study partici- ing the largest set of unrelated individuals. All SNPs were then pants included families from previous studies of OM conducted tested for departures from Hardy-Weinberg proportions. With by the Otitis Media Research Center at the University of Minne- multiple SNPs genotyped in the FBXO11 gene, the haplotype sota,Minneapolis,themembersofthegeneralpublicwhoresponded block structure and linkage disequilibrium (LD) between mark- to fliers posted around the university’s Academic Health Center, ers was assessed. Estimates of LD (DЈ and r2) were computed and otolaryngology clinic patients. Prospective families from pre- also using the largest set of unrelated individuals and Dprime vious studies were identified using OM history data collected in software. For families in which no founder was genotyped, the the original study on the participant (proband), parents, and sib- first affected offspring was used to estimate the statistics. lings. Mothers from the families recruited from the general pub- Association between individual SNP and COME/ROM sta- lic and clinic patients were interviewed about the OM history of tus was performed using a series of generalized estimating equa- all family members to determine family eligibility. Data were col- tion models.26 We adjusted for the correlation between sub- lected at the study visit to determine phenotype (history of chronic jects within a pedigree in the analyses by assuming exchangeable OM or ROM), including findings from the otomicroscopic exami- correlation among siblings within a pedigree and computing nation, multifrequency tympanometry, reported OM history, and 13 the sandwich estimator of the variance. The sandwich estima- medical record. An individual was considered to be affected if tor is also denoted the robust or empirical estimator of the vari- at least 2 of these sources had abnormal findings, or if 1 source ance and is robust to misspecification of the correlation ma- showed abnormalities and middle ear or tympanometric findings trix because it estimates the within-pedigree correlation matrix were presumed to be definitive evidence of a history of COME/ from the first and second moments of the data. Broadly speak- ROM (eg, tympanosclerosis, atrophy, or tympanogram with high ing, this method is comparable to a logistic regression analysis static admittance) were present. Subjects were examined by a neu- with adjustment for familial correlation among family mem- rotologist, and those with obvious craniofacial anomalies were ex- bers.
Load more

Recommended publications
  • (Ubl-Ptms): Small Peptides with Huge Impact in Liver Fibrosis
    cells Review Ubiquitin-Like Post-Translational Modifications (Ubl-PTMs): Small Peptides with Huge Impact in Liver Fibrosis 1 1, 1, Sofia Lachiondo-Ortega , Maria Mercado-Gómez y, Marina Serrano-Maciá y , Fernando Lopitz-Otsoa 2, Tanya B Salas-Villalobos 3, Marta Varela-Rey 1, Teresa C. Delgado 1,* and María Luz Martínez-Chantar 1 1 Liver Disease Lab, CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Spain; [email protected] (S.L.-O.); [email protected] (M.M.-G.); [email protected] (M.S.-M.); [email protected] (M.V.-R.); [email protected] (M.L.M.-C.) 2 Liver Metabolism Lab, CIC bioGUNE, 48160 Derio, Spain; fl[email protected] 3 Department of Biochemistry and Molecular Medicine, School of Medicine, Autonomous University of Nuevo León, Monterrey, Nuevo León 66450, Mexico; [email protected] * Correspondence: [email protected]; Tel.: +34-944-061318; Fax: +34-944-061301 These authors contributed equally to this work. y Received: 6 November 2019; Accepted: 1 December 2019; Published: 4 December 2019 Abstract: Liver fibrosis is characterized by the excessive deposition of extracellular matrix proteins including collagen that occurs in most types of chronic liver disease. Even though our knowledge of the cellular and molecular mechanisms of liver fibrosis has deeply improved in the last years, therapeutic approaches for liver fibrosis remain limited. Profiling and characterization of the post-translational modifications (PTMs) of proteins, and more specifically NEDDylation and SUMOylation ubiquitin-like (Ubls) modifications, can provide a better understanding of the liver fibrosis pathology as well as novel and more effective therapeutic approaches.
    [Show full text]
  • DRE-1/FBXO11, a Conserved F Box Protein, Regulates Apoptosis in C
    Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2011 DRE-1/FBXO11, A Conserved F Box Protein, Regulates Apoptosis in C. elegans and is Mutated in Human Lymphoma Michael Chiorazzi Follow this and additional works at: http://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons Recommended Citation Chiorazzi, Michael, "DRE-1/FBXO11, A Conserved F Box Protein, Regulates Apoptosis in C. elegans and is Mutated in Human Lymphoma" (2011). Student Theses and Dissertations. Paper 139. This Thesis is brought to you for free and open access by Digital Commons @ RU. It has been accepted for inclusion in Student Theses and Dissertations by an authorized administrator of Digital Commons @ RU. For more information, please contact [email protected]. DRE-1/FBXO11, A CONSERVED F BOX PROTEIN, REGULATES APOPTOSIS IN C. ELEGANS AND IS MUTATED IN HUMAN LYMPHOMA A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Michael Chiorazzi June 2011 © Copyright by Michael Chiorazzi 2011 DRE-1/FBXO11, a conserved F box protein, regulates apoptosis in C. elegans and is mutated in human lymphoma Michael Chiorazzi, Ph.D. The Rockefeller University 2011 In the course of metazoan embryonic and post-embryonic development, more cells are generated than exist in the mature organism, and these cells are deleted by the process of programmed cell death. In addition, cells can be pushed toward death when they accumulate genetic errors, are virally-infected or are otherwise deemed potentially-harmful to the overall organism. Caenorhabditis elegans has proved to be an excellent model system for elucidating the genetic underpinnings of cell death, and research has shown that the core machinery, made up of the egl-1, ced-9, ced-4 and ced-3 genes, is conserved across metazoans, and their homologues are crucial for such diseases as cancer, neurodegeneration and autoimmunity.
    [Show full text]
  • Molecular Players Affecting the Biological Timer System to Determine Pupation Timing in Drosophila
    Molecular players affecting the biological timer system to determine pupation timing in Drosophila ショウジョウバエの蛹化タイミングを決める 生物タイマーシステムに影響を及ぼす分子 September 2018 Hamdy Aly Mohamed Aly The Graduate School of Natural Science and Technology (Doctor’s Course) Okayama University ACKNOWLEDGMENTS First of all, I would like to thank my supervisor Prof. Hitoshi Ueda for giving me the opportunity of being in Japan to performing my Ph.D. in his laboratory. I am very grateful to you for advice, guidance, valuable comments, for your suggestions and for your didactic way in clarifying the ideas, because of you, I have learned how to always think with a scientific essence. A special appreciation is extended to the Japanese Ministry of Education, Culture, Sports, Science, and Technology for providing me the financial assistance which kept away the irritating sensation of financial instability. In our days when role models have become fewer and fewer, I had the privilege of being shaped by an intelligent researcher, Dr. Moustafa Sarhan. I gratefully acknowledge Dr. Moustafa, my mentor, and my best friend, whose passion for helping sets new standards for anyone involved in training and development, or any other endeavor in which one human being seeks to support the growth and improvement of another. I would also like to thank all previous and current members of our laboratory especially Haruka Takase, Shiho Koyama, Koichi Miyagawa, Mayo Nakanishi for their help and for providing useful comments during my research. Special thanks to Dr. Haruka Nishida who helped me to set up my stay and take care of every single detail to make my life more enjoyable in Japan.
    [Show full text]
  • The Regulation of Snail: on the Ubiquitin Edge Qian Yu University of Kentucky, [email protected]
    University of Kentucky UKnowledge Pharmacology and Nutritional Sciences Faculty Pharmacology and Nutritional Sciences Publications 7-3-2017 The Regulation of Snail: On the Ubiquitin Edge Qian Yu University of Kentucky, [email protected] Binhua P. Zhou University of Kentucky, [email protected] Yadi Wu University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/pharmacol_facpub Part of the Cancer Biology Commons, Cell Biology Commons, and the Microbiology Commons Repository Citation Yu, Qian; Zhou, Binhua P.; and Wu, Yadi, "The Regulation of Snail: On the Ubiquitin Edge" (2017). Pharmacology and Nutritional Sciences Faculty Publications. 62. https://uknowledge.uky.edu/pharmacol_facpub/62 This Article is brought to you for free and open access by the Pharmacology and Nutritional Sciences at UKnowledge. It has been accepted for inclusion in Pharmacology and Nutritional Sciences Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact [email protected]. The Regulation of Snail: On the Ubiquitin Edge Notes/Citation Information Published in Cancer Cell & Microenvironment, v. 4, no. 2, e1567, p. 1-5. © 2017 The Authors Licensed under a Creative Commons Attribution 4.0 International License which allows users including authors of articles to copy and redistribute the material in any medium or format, in addition to remix, transform, and build upon the material for any purpose, even commercially, as long as the author and original source are properly cited or credited.
    [Show full text]
  • FBXO11 (C) Antibody, Rabbit Polyclonal
    Order: (888)-282-5810 (Phone) (818)-707-0392 (Fax) [email protected] Web: www.Abiocode.com FBXO11 (C) Antibody, Rabbit Polyclonal Cat#: R0957-2 Lot#: Refer to vial Quantity: 100 ul Application: WB Predicted I Observed M.W.: 104 I 130 kDa Uniprot ID: Q86XK2 Background: F-box only protein 11 (FBXo11) is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2 and BCL6. The SCF (FBXO11) complex mediates ubiquitination and degradation of BCL6, thereby playing a role in the germinal center B-cells terminal differentiation toward memory B-cells and plasma cells. The SCF (FBXO11) complex also mediates ubiquitination and degradation of DTL, an important step for the regulation of TGF-beta signaling, cell migration and the timing of the cell-cycle progression and exit. FBXO11 binds to and neddylates phosphorylated p53/TP53, inhibiting its transcriptional activity. Other Names: F-box only protein 11, Protein arginine N-methyltransferase 9, Vitiligo-associated protein 1, VIT-1, FBX11, PRMT9, VIT1 Source and Purity: Rabbit polyclonal antibodies were produced by immunizing animals with a GST-fusion protein containing the C-terminal region of human FBXO11. Antibodies were purified by affinity purification using immunogen. Storage Buffer and Condition: Supplied in 1 x PBS (pH 7.4), 100 ug/ml BSA, 40% Glycerol, 0.01% NaN3. Store at -20 °C. Stable for 6 months from date of receipt. Species Specificity: Human Tested Applications: WB: 1:1,000-1:3,000 (detect endogenous protein*) *: The apparent protein size on WB may be different from the calculated M.W.
    [Show full text]
  • The Role of VIT1/FBXO11 in the Regulation of Apoptosis and Tyrosinase Export from Endoplasmic Reticulum in Cultured Melanocytes
    57-65.qxd 20/5/2010 09:38 Ì ™ÂÏ›‰·57 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 26: 57-65, 2010 57 The role of VIT1/FBXO11 in the regulation of apoptosis and tyrosinase export from endoplasmic reticulum in cultured melanocytes CUIPING GUAN1, FUQUAN LIN2, MIAONI ZHOU1, WEISONG HONG1, LIFANG FU1, WEN XU1, DONGYIN LIU1, YINSHENG WAN3 and AIE XU1 1Department of Dermatology, Third People's Hospital of Hangzhou, Hangzhou 310009; 2Bioengineering Institute, Zhejiang Sci-Tech University, Hangzhou 310018, P.R. China; 3Department of Biology, Providence College, Providence, RI 02918, USA Received January 11, 2010; Accepted March 10, 2010 DOI: 10.3892/ijmm_00000435 Abstract. Our previous study has shown that VIT1 gene in Large population surveys have shown a prevalence ranging Chinese vitiligo patients is de facto the FBXO11 gene, and from 0.38 to 1.13% (1). Why and how melanocytes disappear the silencing of that gene has an impact on the ultrastructure to induce the characteristic achromic lesions is not fully of melanocytes. In this study, we further identified the role of understood. Current consensus regarding the etiology of the FBXO11 gene in melanocytes and the relationship vitiligo implies a progressive loss of pigment cells. between dilated endoplasmic reticulum (ER) and tyrosinase Although the pathogenesis of vitiligo cannot be explained by inhibition and overexpression of FBXO11 gene. Cell by genetics clearly, linkage and association studies have proliferation, apoptosis, cycle and migration of melanocytes begun to provide strong support for vitiligo susceptibility were examined when the FBXO11 gene was silenced or genes on chromosomes 4q13-q21, 1p31, 7q22, 8p12 and 17p13 overexpressed.
    [Show full text]
  • The Post-Translational Regulation of Epithelial–Mesenchymal Transition-Inducing Transcription Factors in Cancer Metastasis
    International Journal of Molecular Sciences Review The Post-Translational Regulation of Epithelial–Mesenchymal Transition-Inducing Transcription Factors in Cancer Metastasis Eunjeong Kang † , Jihye Seo † , Haelim Yoon and Sayeon Cho * Laboratory of Molecular and Pharmacological Cell Biology, College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; [email protected] (E.K.); [email protected] (J.S.); [email protected] (H.Y.) * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Epithelial–mesenchymal transition (EMT) is generally observed in normal embryogenesis and wound healing. However, this process can occur in cancer cells and lead to metastasis. The contribution of EMT in both development and pathology has been studied widely. This transition requires the up- and down-regulation of specific proteins, both of which are regulated by EMT- inducing transcription factors (EMT-TFs), mainly represented by the families of Snail, Twist, and ZEB proteins. This review highlights the roles of key EMT-TFs and their post-translational regulation in cancer metastasis. Keywords: metastasis; epithelial–mesenchymal transition; transcription factor; Snail; Twist; ZEB Citation: Kang, E.; Seo, J.; Yoon, H.; 1. Introduction Cho, S. The Post-Translational Morphological alteration in tissues is related to phenotypic changes in cells [1]. Regulation of Changes in morphology and functions of cells can be caused by changes in transcrip- Epithelial–Mesenchymal tional programs and protein expression [2]. One such change is epithelial–mesenchymal Transition-Inducing Transcription transition (EMT). Factors in Cancer Metastasis. Int. J. EMT is a natural trans-differentiation program of epithelial cells into mesenchymal Mol. Sci. 2021, 22, 3591. https:// cells [2]. EMT is primarily related to normal embryogenesis, including gastrulation, renal doi.org/10.3390/ijms22073591 development, formation of the neural crest, and heart development [3].
    [Show full text]
  • The Role of Ubiquitination and Sumoylation in DNA Replication
    The Role of Ubiquitination and SUMOylation in DNA Replication Tarek Abbas1,2,3* 1Department of Radiation Oncology, University of Virginia, Charlotesville, VA, USA. 2Department of Biochemistry and Molecular Genetics, University of Virginia, Charlotesville, VA, USA. 3Center for Cell Signaling, University of Virginia, Charlotesville, VA, USA. *Correspondence: [email protected] htps://doi.org/10.21775/cimb.040.189 Abstract Regulation of eukaryotic DNA DNA replication is a tightly regulated conserved replication process that ensures the faithful transmission of genetic material to defne heritable phenotypic Initiation of DNA replication traits. Perturbations in this process result in Eukaryotic DNA replication is tightly regulated genomic instability, mutagenesis, and diseases, such that cells replicate their entire genome once including malignancy. Proteins involved in the and only once in a given cell cycle (Machida et initiation, progression, and termination of DNA al., 2005). For mammalian cells, this is no easy replication are subject to a plethora of revers- task since each proliferative somatic cell must ef- ible post-translational modifcations (PTMs) to ciently replicate approximately 6 billion base pairs provide a proper temporal and spatial control (in male cells) from roughly 250,000 replication of replication. Among these, modifcations origins scatered throughout the genome with involving the covalent atachment of the small each division cycle (Cadoret et al., 2008; Sequeira- protein ubiquitin or the small ubiquitin-like Mendes et al., 2009; Karnani et al., 2010). With modifer (SUMO) to replication and replication- roughly 600 million new blood cells born in the associated proteins are particularly important for bone marrow of an adult human (Doulatov et al., the proper regulation of DNA replication as well 2012), one cannot grasp the magnitude of the as for optimal cellular responses to replication task the replication machinery has to accomplish.
    [Show full text]
  • Role of the Ubiquitin Proteasome System in Hematologic Malignancies
    Anagh A. Sahasrabuddhe Role of the ubiquitin proteasome Kojo S. J. Elenitoba-Johnson system in hematologic malignancies Authors’ address Summary: Ubiquitination is a post-translational modification process Anagh A. Sahasrabuddhe1, Kojo S. J. Elenitoba-Johnson1 that regulates several critical cellular processes. Ubiquitination is 1Department of Pathology, University of Michigan, Ann orchestrated by the ubiquitin proteasome system (UPS), which consti- Arbor, MI, USA. tutes a cascade of enzymes that transfer ubiquitin onto protein sub- strates. The UPS catalyzes the destruction of many critical protein Correspondence to: substrates involved in cancer pathogenesis. This review article focuses Kojo S. J. Elenitoba-Johnson on components of the UPS that have been demonstrated to be deregu- Department of Pathology lated by a variety of mechanisms in hematologic malignancies. These University of Michigan include E3 ubiquitin ligases and deubiquitinating enzymes. The pros- 2037 BSRB 109 Zina Pitcher Place pects of specific targeting of key enzymes in this pathway that are criti- Ann Arbor, MI 48109, USA cal to the pathogenesis of particular hematologic neoplasia are also Tel.: +1 734 615 4388 discussed. Fax: +1 734 615 9666 e-mail: [email protected] Keywords: ubiquitin-proteasome system, hematologic malignancy, E3 ligase, deubiqu- itinases Acknowledgements This work was supported in part by NIH grants R01 DE119249, and R01 CA136905 to KSJ E-J. The authors The ubiquitin proteasome system declare no conflicts of interest. The ubiquitin proteasome system (UPS) is the major degra- dation machinery that controls the abundance of critical cel- This article is part of a series of reviews lular regulatory proteins through a stepwise cascade covering Hematologic Malignancies appearing in Volume 263 of Immunological consisting of a ubiquitin activating enzyme or UBA (E1), Reviews.
    [Show full text]
  • C/EBPB-Dependent Adaptation to Palmitic Acid Promotes Stemness in Hormone Receptor Negative Breast Cancer
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.11.244509; this version posted August 11, 2020. 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. C/EBPB-dependent Adaptation to Palmitic Acid Promotes Stemness in Hormone Receptor Negative Breast Cancer Xiao-Zheng Liu1,7, Anastasiia Rulina1,7, Man Hung Choi2,3, Line Pedersen1, Johanna Lepland1, Noelly Madeleine1, Stacey D’mello Peters1, Cara Ellen Wogsland1, Sturla Magnus Grøndal1, James B Lorens1, Hani Goodarzi4, Anders Molven2,3, Per E Lønning5,6, Stian KnappsKog5,6, Nils Halberg1,* 1Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway 2Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, N-5020 Bergen, Norway 3Department of Pathology, HauKeland University Hospital, N-5021 Bergen, Norway 4Department of Biophysics and Biochemistry, University of California San Francisco, San Francisco, CA 94158, USA 5Department of Clinical Science, Faculty of Medicine, University of Bergen, N-5020 Bergen, Norway 6Department of Oncology, HauKeland University Hospital, N-5021 Bergen, Norway 7These authors contributed equally *Correspondence: Nils Halberg Department of Biomedicine University of Bergen Jonas Lies vei 91 5020 Bergen, Norway Phone: +47 5558 6442 Email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.11.244509; this version posted August 11, 2020. 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. Abstract Epidemiological studies have established a positive association between obesity and the incidence of postmenopausal (PM) breast cancer.
    [Show full text]
  • Atlas Journal
    Atlas of Genetics and Cytogenetics in Oncology and Haematology Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Portal Teaching X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA Atlas Journal Atlas Journal versus Atlas Database: the accumulation of the issues of the Journal constitutes the body of the Database/Text-Book. TABLE OF CONTENTS Volume 11, Number 3, Jul-Sep 2007 Previous Issue / Next Issue Genes MSH6 (mutS homolog 6 (E. Coli)) (2p16). Sreeparna Banerjee. Atlas Genet Cytogenet Oncol Haematol 2006; 9 11 (3): 289-297. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/MSH6ID344ch2p16.html LDB1 (10q24). Takeshi Setogawa, Testu Akiyama. Atlas Genet Cytogenet Oncol Haematol 2006; 11 (3): 298-301.[Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/LDB1ID41135ch10q24.html INTS6 (integrator complex subunit 6) (13q14.3). Ilse Wieland. Atlas Genet Cytogenet Oncol Haematol 2006; 11 (3): 302-306.[Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/INTS6ID40287ch13q14.html EPHA7 (EPH receptor A7) (6q16.1). Haruhiko Sugimura, Hiroki Mori, Tomoyasu Bunai, Masaya Suzuki. Atlas Genet Cytogenet Oncol Haematol 2007; 11 (3): 307-312. [Full Text] [PDF] Atlas Genet Cytogenet Oncol Haematol 2007;3 -I URL : http://atlasgeneticsoncology.org/Genes/EPHA7ID40466ch6q16.html RNASET2 (ribonuclease T2) (6q27). Francesco Acquati, Paola Campomenosi. Atlas Genet Cytogenet Oncol Haematol 2007; 11 (3): 313-317. [Full Text] [PDF] URL : http://atlasgeneticsoncology.org/Genes/RNASET2ID518ch6q27.html RHOB (ras homolog gene family, member B) (2p24.1). Minzhou Huang, Lisa D Laury-Kleintop, George Prendergast. Atlas Genet Cytogenet Oncol Haematol 2007; 11 (3): 318-323.
    [Show full text]
  • Cellular Immunology E3 Ubiquitin Ligases in B-Cell Malignancies
    Cellular Immunology 340 (2019) 103905 Contents lists available at ScienceDirect Cellular Immunology journal homepage: www.elsevier.com/locate/ycimm Research paper E3 ubiquitin ligases in B-cell malignancies T ⁎ Jaewoo Choi1, Luca Busino Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA SUMMARY Ubiquitylation is a post-translational modification (PTM) that controls various cellular signaling pathways. It is orchestrated by a three-step enzymatic cascadeknow as the ubiquitin proteasome system (UPS). E3 ligases dictate the specificity to the substrates, primarily leading to proteasome-dependent degradation. Deregulation of the UPS components by various mechanisms contributes to the pathogenesis of cancer. This review focuses on E3 ligase-substrates pairings that are implicated in B- cell malignancies. Understanding the molecular mechanism of specific E3 ubiquitin ligases will present potential opportunities for the development oftargeted therapeutic approaches. 1. The ubiquitin proteasome system degradation [7,8]. On the other hand, Lys-63-linked chains regulate DNA repair, endocytic trafficking, NF-κB activation, and assembling a The ubiquitin proteasome system (UPS) plays a significant role in signaling complex for mRNA translation [9–12]. M-linked chains or the regulation of cell growth and survival, in addition to maintaining linear ubiquitin chains play an important role in immune, inflammatory cellular homeostasis. By means of the UPS, cells can precisely and and NF-κB signaling [13–15]. The significance and the roles of Lys6-, temporally degrade approximately 80% of the entire proteome. Lys27-, Lys29-, Lys33- linked chains are still poorly understood al- However, failure to do so results in numerous diseases, including he- though, recently, they have been implicated in DNA repair, trans-Golgi matological malignancies and cancer [1–3].
    [Show full text]