Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia
Abstract
Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involved in innate and adaptive immunity. Although dysregulation in ubiquitin molecular processes is central to the pathogenesis of multiple human diseases, the expression patterns of ubiquitination genes in SMA remain unexplored. Methods: To examine the role of the ubiquitination processes in pathogenesis of SMA, differential gene expression profiles were determined in Kenyan children ( n = 44, aged <48 mos) with either mild malarial anemia (M l MA; Hb ≥9.0 g/dl; n = 23) or SMA (Hb <6.0 g/dl; n = 21) using the Qiagen Human Ubiquitination Pathway RT 2 Profiler PCR Array containing a set of 84 human ubiquitination genes. Results: In children with SMA, 10 genes were down-regulated ( BRCC3 , FBXO3 , MARCH5 , RFWD2 , SMURF2 , UBA6 , UBE2A , UBE2D1 , UBE2L3 , UBR1 ), and five genes were up-regulated ( MDM2 , PARK2 , STUB1 , UBE2E3 , UBE2M ). Enrichment analyses revealed Ubiquitin-Proteasomal Proteolysis as the top disrupted process,more »
- Authors:
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1832037
- Resource Type:
- Published Article
- Journal Name:
- Frontiers in Genetics
- Additional Journal Information:
- Journal Name: Frontiers in Genetics Journal Volume: 12; Journal ID: ISSN 1664-8021
- Publisher:
- Frontiers Media SA
- Country of Publication:
- Switzerland
- Language:
- English
Citation Formats
Anyona, Samuel B., Raballah, Evans, Cheng, Qiuying, Hurwitz, Ivy, Ndege, Caroline, Munde, Elly, Otieno, Walter, Seidenberg, Philip D., Schneider, Kristan A., Lambert, Christophe G., McMahon, Benjamin H., Ouma, Collins, and Perkins, Douglas J. Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia. Switzerland: N. p., 2021.
Web. doi:10.3389/fgene.2021.764759.
Anyona, Samuel B., Raballah, Evans, Cheng, Qiuying, Hurwitz, Ivy, Ndege, Caroline, Munde, Elly, Otieno, Walter, Seidenberg, Philip D., Schneider, Kristan A., Lambert, Christophe G., McMahon, Benjamin H., Ouma, Collins, & Perkins, Douglas J. Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia. Switzerland. https://doi.org/10.3389/fgene.2021.764759
Anyona, Samuel B., Raballah, Evans, Cheng, Qiuying, Hurwitz, Ivy, Ndege, Caroline, Munde, Elly, Otieno, Walter, Seidenberg, Philip D., Schneider, Kristan A., Lambert, Christophe G., McMahon, Benjamin H., Ouma, Collins, and Perkins, Douglas J. Mon .
"Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia". Switzerland. https://doi.org/10.3389/fgene.2021.764759.
@article{osti_1832037,
title = {Differential Gene Expression in Host Ubiquitination Processes in Childhood Malarial Anemia},
author = {Anyona, Samuel B. and Raballah, Evans and Cheng, Qiuying and Hurwitz, Ivy and Ndege, Caroline and Munde, Elly and Otieno, Walter and Seidenberg, Philip D. and Schneider, Kristan A. and Lambert, Christophe G. and McMahon, Benjamin H. and Ouma, Collins and Perkins, Douglas J.},
abstractNote = {Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involved in innate and adaptive immunity. Although dysregulation in ubiquitin molecular processes is central to the pathogenesis of multiple human diseases, the expression patterns of ubiquitination genes in SMA remain unexplored. Methods: To examine the role of the ubiquitination processes in pathogenesis of SMA, differential gene expression profiles were determined in Kenyan children ( n = 44, aged <48 mos) with either mild malarial anemia (M l MA; Hb ≥9.0 g/dl; n = 23) or SMA (Hb <6.0 g/dl; n = 21) using the Qiagen Human Ubiquitination Pathway RT 2 Profiler PCR Array containing a set of 84 human ubiquitination genes. Results: In children with SMA, 10 genes were down-regulated ( BRCC3 , FBXO3 , MARCH5 , RFWD2 , SMURF2 , UBA6 , UBE2A , UBE2D1 , UBE2L3 , UBR1 ), and five genes were up-regulated ( MDM2 , PARK2 , STUB1 , UBE2E3 , UBE2M ). Enrichment analyses revealed Ubiquitin-Proteasomal Proteolysis as the top disrupted process, along with altered sub-networks involved in proteasomal, protein, and ubiquitin-dependent catabolic processes. Conclusion: Collectively, these novel results show that protein coding genes of the ubiquitination processes are involved in the pathogenesis of SMA.},
doi = {10.3389/fgene.2021.764759},
journal = {Frontiers in Genetics},
number = ,
volume = 12,
place = {Switzerland},
year = {Mon Nov 22 00:00:00 EST 2021},
month = {Mon Nov 22 00:00:00 EST 2021}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.3389/fgene.2021.764759
https://doi.org/10.3389/fgene.2021.764759
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Hemolysis Is Associated with Low Reticulocyte Production Index and Predicts Blood Transfusion in Severe Malarial Anemia
journal, April 2010
- Fendel, Rolf; Brandts, Christian; Rudat, Annika
- PLoS ONE, Vol. 5, Issue 4
Mechanisms Underlying Ubiquitination
journal, June 2001
- Pickart, Cecile M.
- Annual Review of Biochemistry, Vol. 70, Issue 1
Mechanical Fluctuations of the Membrane–Skeleton Are Dependent on F-Actin ATPase in Human Erythrocytes
journal, June 1998
- Tuvia, Shmuel; Levin, Shlomo; Bitler, Arkady
- Journal of Cell Biology, Vol. 141, Issue 7
β‐Adrenergic agonists regulate cell membrane fluctuations of human erythrocytes
journal, May 1999
- Tuvia, Shmuel; Moses, Ayelet; Gulayev, Nathan
- The Journal of Physiology, Vol. 516, Issue 3
Hematological predictors of increased severe anemia in Kenyan children coinfected with Plasmodium falciparum and HIV-1
journal, April 2010
- Davenport, Gregory C.; Ouma, Collins; Hittner, James B.
- American Journal of Hematology, Vol. 85, Issue 4
The intolerable burden of malaria: a new look at the numbers
journal, January 2001
- Breman, Jg; Egan, A.; Keusch, Gt
- The American Journal of Tropical Medicine and Hygiene, Vol. 64, Issue 1_suppl
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
journal, April 2002
- Glickman, Michael H.; Ciechanover, Aaron
- Physiological Reviews, Vol. 82, Issue 2
Higher resistance to Plasmodium falciparum infection in patients with homozygous sickle cell disease in western Kenya
journal, June 1997
- Aluoch, J. R.
- Tropical Medicine & International Health, Vol. 2, Issue 6
Malaria investigation and treatment of children admitted to county hospitals in western Kenya
journal, October 2016
- Amboko, Beatrice I.; Ayieko, Philip; Ogero, Morris
- Malaria Journal, Vol. 15, Issue 1
Changing malaria intervention coverage, transmission and hospitalization in Kenya
journal, October 2010
- Okiro, Emelda A.; Alegana, Victor A.; Noor, Abdisalan M.
- Malaria Journal, Vol. 9, Issue 1
Immunological processes underlying the slow acquisition of humoral immunity to malaria
journal, January 2016
- Ryg-Cornejo, Victoria; Ly, Ann; Hansen, Diana S.
- Parasitology, Vol. 143, Issue 2
Molecular basis of reduced LAIR1 expression in childhood severe malarial anaemia: Implications for leukocyte inhibitory signalling
journal, July 2019
- Achieng, Angela O.; Guyah, Bernard; Cheng, Qiuying
- EBioMedicine, Vol. 45
Structure and Functions of the 20S and 26S Proteasomes
journal, June 1996
- Coux, Olivier; Tanaka, Keiji; Goldberg, Alfred L.
- Annual Review of Biochemistry, Vol. 65, Issue 1
Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria
journal, January 2006
- Otieno, Richard O.; Ouma, Collins; Ongʼecha, John M.
- AIDS, Vol. 20, Issue 2
Ubiquitin and Proteasomes in Transcription
journal, July 2012
- Geng, Fuqiang; Wenzel, Sabine; Tansey, William P.
- Annual Review of Biochemistry, Vol. 81, Issue 1
Mechanisms of naturally acquired immunity to P. falciparum and approaches to identify merozoite antigen targets
journal, November 2017
- Healer, Julie; Chiu, Chris Y.; Hansen, Diana S.
- Parasitology, Vol. 145, Issue 7
Identification of Inflammatory Biomarkers for Pediatric Malarial Anemia Severity Using Novel Statistical Methods
journal, August 2011
- Ong'echa, John M.; Davenport, Gregory C.; Vulule, John M.
- Infection and Immunity, Vol. 79, Issue 11
Rapid degradation of a large fraction of newly synthesized proteins by proteasomes
journal, April 2000
- Schubert, Ulrich; Antón, Luis C.; Gibbs, James
- Nature, Vol. 404, Issue 6779
Pathway for Degradation of Peptides Generated by Proteasomes
journal, November 2004
- Saric, Tomo; Graef, Claudia I.; Goldberg, Alfred L.
- Journal of Biological Chemistry, Vol. 279, Issue 45
Deubiquitinating enzymes regulate PARK2-mediated mitophagy
journal, April 2015
- Wang, Yuqing; Serricchio, Mauro; Jauregui, Miluska
- Autophagy, Vol. 11, Issue 4
Mdm2 promotes the rapid degradation of p53
journal, May 1997
- Haupt, Ygal; Maya, Ruth; Kazaz, Anat
- Nature, Vol. 387, Issue 6630
Regulation of red blood cell filterability by Ca 2+ influx and cAMP-mediated signaling pathways
journal, December 1997
- Oonishi, Tadahiro; Sakashita, Kanako; Uyesaka, Nobuhiro
- American Journal of Physiology-Cell Physiology, Vol. 273, Issue 6
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
journal, December 2001
- Livak, Kenneth J.; Schmittgen, Thomas D.
- Methods, Vol. 25, Issue 4
Redox Regulation via Glutaredoxin-1 and Protein S -Glutathionylation
journal, April 2020
- Matsui, Reiko; Ferran, Beatriz; Oh, Albin
- Antioxidants & Redox Signaling, Vol. 32, Issue 10
The ubiquitin-proteasome pathway: on protein death and cell life
journal, December 1998
- Ciechanover, A.
- The EMBO Journal, Vol. 17, Issue 24
Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes
journal, November 2011
- Sadowski, Martin; Suryadinata, Randy; Tan, Anthonius Ricardo
- IUBMB Life, Vol. 64, Issue 2
Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins
journal, October 2017
- Seissler, Tanja; Marquet, Roland; Paillart, Jean-Christophe
- Viruses, Vol. 9, Issue 11
Proteolysis: from the lysosome to ubiquitin and the proteasome
journal, January 2005
- Ciechanover, Aaron
- Nature Reviews Molecular Cell Biology, Vol. 6, Issue 1
Proteasomes: destruction as a programme
journal, March 1996
- Hilt, Wolfgang; Wolf, Dieter H.
- Trends in Biochemical Sciences, Vol. 21, Issue 3
Childhood cause-specific mortality in rural Western Kenya: application of the InterVA-4 model
journal, October 2014
- Amek, Nyaguara O.; Odhiambo, Frank O.; Khagayi, Sammy
- Global Health Action, Vol. 7, Issue 1
Ubiquitin and ubiquitin-like specific proteases targeted by infectious pathogens: Emerging patterns and molecular principles
journal, December 2008
- Edelmann, Mariola J.; Kessler, Benedikt M.
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1782, Issue 12
Targeting of substrates to the 26S proteasome
journal, November 1997
- Pickart, Cecile M.
- The FASEB Journal, Vol. 11, Issue 13
Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children.
journal, April 1999
- Roberts, J. M.; Nahlen, B.; Lal, A.
- The American Journal of Tropical Medicine and Hygiene, Vol. 60, Issue 4
New insights into ubiquitin E3 ligase mechanism
journal, April 2014
- Berndsen, Christopher E.; Wolberger, Cynthia
- Nature Structural & Molecular Biology, Vol. 21, Issue 4
Ubiquitination in disease pathogenesis and treatment
journal, November 2014
- Popovic, Doris; Vucic, Domagoj; Dikic, Ivan
- Nature Medicine, Vol. 20, Issue 11
Extracellular, circulating proteasomes and ubiquitin — Incidence and relevance
journal, December 2008
- Sixt, Stephan U.; Dahlmann, Burkhardt
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1782, Issue 12
Hb Kenya among Luo Adults and Young Children in Malaria Holoendemic Western Kenya: Screened by High Performance Liquid Chromatography and Confirmed By Polymerase Chain Reaction
journal, January 2007
- Kifude, Carolyne M.; Polhemus, Mark E.; Heppner, D. Gray
- Hemoglobin, Vol. 31, Issue 4
Analysis of repeated hemoglobin measures in full-term, normal birth weight Kenyan children between birth and four years of age. III. The Asemobo Bay Cohort Project.
journal, December 1999
- Kuile, F. O.; Nahlen, B. L.; Bloland, P. B.
- The American Journal of Tropical Medicine and Hygiene, Vol. 61, Issue 6
Ubiquitin: structures, functions, mechanisms
journal, November 2004
- Pickart, Cecile M.; Eddins, Michael J.
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1695, Issue 1-3
Severe Malarial Anemia: Innate Immunity and Pathogenesis
journal, January 2011
- Perkins, Douglas J.; Were, Tom; Davenport, Gregory C.
- International Journal of Biological Sciences, Vol. 7, Issue 9
The Proteasome: From Basic Mechanisms to Emerging Roles
journal, January 2013
- Tanaka, Keiji
- The Keio Journal of Medicine, Vol. 62, Issue 1
Ubiquitin and proteasome gene expression is increased in skeletal muscle of slim AIDS patients.
journal, July 1998
- Llovera, M.; Garcia-Martinez, C.; Agell, N.
- International Journal of Molecular Medicine
A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation
journal, October 2019
- Tran, Tuan M.; Guha, Rajan; Portugal, Silvia
- Immunity, Vol. 51, Issue 4
Infant and child mortality in relation to malaria transmission in KEMRI/CDC HDSS, Western Kenya: validation of verbal autopsy
journal, January 2018
- Amek, Nyaguara O.; Van Eijk, Annemieke; Lindblade, Kim A.
- Malaria Journal, Vol. 17, Issue 1
In-Hospital Morbidity and Mortality Due to Severe Malarial Anemia in Western Kenya
journal, December 2007
- Obonyo, Charles O.; Vulule, John; Akhwale, Willis S.
- The American Journal of Tropical Medicine and Hygiene, Vol. 77, Issue 6_Suppl
How the ubiquitin–proteasome system controls transcription
journal, March 2003
- Muratani, Masafumi; Tansey, William P.
- Nature Reviews Molecular Cell Biology, Vol. 4, Issue 3
Parasitemia, Anemia, and Malarial Anemia in Infants and Young Children in a Rural Holoendemic Plasmodium Falciparum Transmission area
journal, March 2006
- Landis-Lewis, Zachary; Keller, Christopher C.; Otieno, Richard O.
- The American Journal of Tropical Medicine and Hygiene, Vol. 74, Issue 3
Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C
journal, January 2006
- Honda, Masao; Yamashita, Taro; Ueda, Teruyuki
- Hepatology, Vol. 44, Issue 5
Outpatient Upper Respiratory Tract Viral Infections in Children with Malaria Symptoms in Western Kenya
journal, November 2010
- Domingo, Gonzalo J.; Neuzil, Kathleen M.; Gerlach, Jay
- The American Journal of Tropical Medicine and Hygiene, Vol. 83, Issue 5
Bacteremia in Kenyan Children Presenting with Malaria
journal, November 2010
- Were, T.; Davenport, G. C.; Hittner, J. B.
- Journal of Clinical Microbiology, Vol. 49, Issue 2
Cyclooxygenase-2 haplotypes influence the longitudinal risk of malaria and severe malarial anemia in Kenyan children from a holoendemic transmission region
journal, October 2019
- Anyona, Samuel B.; Hengartner, Nicolas W.; Raballah, Evans
- Journal of Human Genetics, Vol. 65, Issue 2
The 26S Proteasome: A Molecular Machine Designed for Controlled Proteolysis
journal, June 1999
- Voges, D.; Zwickl, P.; Baumeister, W.
- Annual Review of Biochemistry, Vol. 68, Issue 1
Role of the Ubiquitin Proteasome System in the Heart
journal, March 2013
- Pagan, Julia; Seto, Tiffany; Pagano, Michele
- Circulation Research, Vol. 112, Issue 7
Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
journal, April 2002
- Bucciantini, Monica; Giannoni, Elisa; Chiti, Fabrizio
- Nature, Vol. 416, Issue 6880
Regulation of p53 stability by Mdm2
journal, May 1997
- Kubbutat, Michael H. G.; Jones, Stephen N.; Vousden, Karen H.
- Nature, Vol. 387, Issue 6630
The Proteasome and Its Network: Engineering for Adaptability
journal, March 2019
- Finley, Daniel; Prado, Miguel A.
- Cold Spring Harbor Perspectives in Biology, Vol. 12, Issue 1
Relationship between inflammatory mediator patterns and anemia in HIV-1 positive and exposed children with Plasmodium falciparum malaria
journal, May 2012
- Davenport, Gregory C.; Hittner, James B.; Were, Tom
- American Journal of Hematology, Vol. 87, Issue 7
Protective effects of the sickle cell gene against malaria morbidity and mortality
journal, April 2002
- Aidoo, Michael; Terlouw, Dianne J.; Kolczak, Margarette S.
- The Lancet, Vol. 359, Issue 9314