APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly Affected by LINE-1 Expression

Frontiers in Microbiology
Ananda Ayyappan Jaguva VasudevanWolfgang Goering

Abstract

The most common mutational signature in urothelial carcinoma (UC), the most common type of urinary bladder cancer is assumed to be caused by the misdirected activity of APOBEC3 (A3) cytidine deaminases, especially A3A or A3B, which are known to normally restrict the propagation of exogenous viruses and endogenous retroelements such as LINE-1 (L1). The involvement of A3 proteins in urothelial carcinogenesis is unexpected because, to date, UC is thought to be caused by chemical carcinogens rather than viral activity. Therefore, we explored the relationship between A3 expression and L1 activity, which is generally upregulated in UC. We found that UC cell lines highly express A3B and in some cases A3G, but not A3A, and exhibit corresponding cytidine deamination activity in vitro. While we observed evidence suggesting that L1 expression has a weak positive effect on A3B and A3G expression and A3B promoter activity, neither efficient siRNA-mediated knockdown nor overexpression of functional L1 elements affected catalytic activity of A3 proteins consistently. However, L1 knockdown diminished proliferation of a UC cell line exhibiting robust endogenous L1 expression, but had little impact on a cell line with low L1 expression levels. O...Continue Reading

References

Apr 1, 1988·Molecular and Cellular Biology·J SkowronskiM F Singer
May 1, 1997·Nature Genetics·D M SassamanH H Kazazian
Dec 20, 2002·Experimental Cell Research·Sandra SwiatkowskiWolfgang A Schulz
Apr 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Brook BrouhaHaig H Kazazian
Apr 21, 2004·Nature Structural & Molecular Biology·Qin YuNathaniel R Landau
Aug 7, 2004·Current Biology : CB·Kate N BishopMichael H Malim
Jun 1, 2006·The Journal of Biological Chemistry·Heide MuckenfussCarsten Münk
Jul 21, 2006·Biochemical Pharmacology·Michèle J HoffmannWolfgang A Schulz
Apr 19, 2007·World Journal of Urology·Hans-Helge SeifertWolfgang A Schulz
Jul 20, 2007·Methods in Molecular Biology·Koji ItahanaGoberdhan P Dimri
Sep 30, 2008·Nature Structural & Molecular Biology·Roni NowarskiMoshe Kotler
Oct 16, 2008·Cell·John L Goodier, Haig H Kazazian
Jul 10, 2009·Journal of Virology·Fransje A KoningMichael H Malim
Nov 3, 2010·International Review of Cell and Molecular Biology·Gerald G SchumannAnton A Buzdin
Feb 16, 2011·Mobile DNA·Wenfeng AnJef D Boeke
Aug 11, 2011·Carcinogenesis·Wolfgang GoeringWolfgang A Schulz
Aug 23, 2011·Biochemical and Biophysical Research Communications·William M McDougall, Harold C Smith
Sep 1, 2011·The Journal of Biological Chemistry·Silke WissingWarner C Greene
Nov 5, 2011·Nucleic Acids Research·Julija RaizGerald G Schumann
Jun 7, 2012·Cellular Oncology (Dordrecht)·Annemarie KochWolfgang A Schulz
Jun 30, 2012·Science·Eunjung LeeUNKNOWN Cancer Genome Atlas Research Network
Nov 15, 2012·Scientific Reports·Masanobu ShinoharaAkifumi Takaori-Kondo
Apr 5, 2013·PLoS Genetics·Nemanja Rodić, Kathleen H Burns
Apr 20, 2013·Cancer Research·Roni Nowarski, Moshe Kotler
May 21, 2013·Current Topics in Microbiology and Immunology·Eric W Refsland, Reuben S Harris
Jun 14, 2013·Journal of Virology·Ananda Ayyappan Jaguva VasudevanCarsten Münk
Jun 22, 2013·Biological Chemistry·Ananda Ayyappan Jaguva VasudevanCarsten Münk
Jul 16, 2013·Nature Genetics·Michael B BurnsReuben S Harris
Jul 16, 2013·Nature Genetics·Steven A RobertsDmitry A Gordenin
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton

❮ Previous
Next ❯

Citations

Jan 27, 2019·Scientific Reports·Xiongxiong LiJean-Pierre Vartanian
May 6, 2019·International Journal of Molecular Sciences·Ananda Ayyappan Jaguva VasudevanGünter Niegisch
Aug 30, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Andres M AcostaMichelle S Hirsch
Dec 17, 2020·International Journal of Molecular Sciences·Patcharawalai WhongsiriWolfgang A Schulz
Apr 4, 2021·Viruses·Ananda Ayyappan Jaguva VasudevanCarsten Münk

❮ Previous
Next ❯

Methods Mentioned

BETA
deamination
Reverse Transcription PCR
PCR
transfection
transfections
flow cytometry

Software Mentioned

Graphpad Prism
SPSS Statistics

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.