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A Rabbit Monoclonal Antibody against the Antiviral and Cancer Genomic DNA Mutating Enzyme APOBEC3B

Published on Sep 10, 2019in Antibodies
· DOI :10.3390/antib8030047
William L. Brown21
Estimated H-index: 21
,
Emily K. Law11
Estimated H-index: 11
+ 8 AuthorsReuben S. Harris59
Estimated H-index: 59
Abstract
The DNA cytosine deaminase APOBEC3B (A3B) is normally an antiviral factor in the innate immune response. However, A3B has been implicated in cancer mutagenesis, particularly in solid tumors of the bladder, breast, cervix, head/neck, and lung. Here, we report data on the generation and characterization of a rabbit monoclonal antibody (mAb) for human A3B. One mAb, 5210-87-13, demonstrates utility in multiple applications, including ELISA, immunoblot, immunofluorescence microscopy, and immunohistochemistry. In head-to-head tests with commercial reagents, 5210-87-13 was the only rabbit monoclonal suitable for detecting native A3B and for immunohistochemical quantification of A3B in tumor tissues. This novel mAb has the potential to enable a wide range of fundamental and clinical studies on A3B in human biology and disease.
  • References (74)
  • Citations (1)
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References74
Newest
#1Mahesh Chemudupati (OSU: Ohio State University)H-Index: 4
#2Adam D. Kenney (OSU: Ohio State University)H-Index: 4
Last. Jacob S. Yount (OSU: Ohio State University)H-Index: 23
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Abstract Antiviral restriction factors are cellular proteins that inhibit the entry, replication, or spread of viruses. These proteins are critical components of the innate immune system and function to limit the severity and host range of virus infections. Here we review the current knowledge on the mechanisms of action of several restriction factors that affect multiple viruses at distinct stages of their life cycles. For example, APOBEC3G deaminates cytosines to hypermutate reverse transcribe...
4 CitationsSource
#1Michael A. Carpenter (UMN: University of Minnesota)H-Index: 11
#2Emily K. Law (UMN: University of Minnesota)H-Index: 11
Last. Reuben S. Harris (UMN: University of Minnesota)H-Index: 59
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Abstract A major concern of CRISPR and related genome engineering technologies is off-target mutagenesis from prolonged exposure to Cas9 and related editing enzymes. To help mitigate this concern we added a loxP site to the 3′-LTR of an HIV-based lentiviral vector capable of expressing Cas9/gRNA complexes in a wide variety of mammalian cell types. Transduction of susceptible target cells yields an integrated provirus that expresses the desired Cas9/gRNA complex. The reverse transcription process...
5 CitationsSource
#1Gabriel J. Starrett (UMN: University of Minnesota)H-Index: 16
#2Artur A. Serebrenik (UMN: University of Minnesota)H-Index: 3
Last. Reuben S. Harris (UMN: University of Minnesota)H-Index: 59
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ABSTRACT APOBEC3B is a single-stranded DNA cytosine deaminase with beneficial innate antiviral functions. However, misregulated APOBEC3B can also be detrimental by inflicting APOBEC signature C-to-T and C-to-G mutations in genomic DNA of multiple cancer types. Polyomavirus and papillomavirus oncoproteins induce APOBEC3B overexpression, perhaps to their own benefit, but little is known about the cellular mechanisms hijacked by these viruses to do so. Here we investigate the molecular mechanism of...
3 CitationsSource
#1Ju Youn Lee (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 3
#2Michail Schizas (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 8
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Purpose:Lobular carcinoma in situ (LCIS) is a pre-invasive lesion of the breast. We sought to define its genomic landscape, whether intra-lesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers. Experimental Design: We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically-advanced lesions from 24 patients (nine ductal ca...
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#1Adam Z. ChengH-Index: 3
#2Jaime Yockteng-Melgar (U of T: University of Toronto)H-Index: 1
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The apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like (APOBEC) family of single-stranded DNA (ssDNA) cytosine deaminases provides innate immunity against virus and transposon replication1–4. A well-studied mechanism is APOBEC3G restriction of human immunodeficiency virus type 1, which is counteracted by a virus-encoded degradation mechanism1–4. Accordingly, most work has focused on retroviruses with obligate ssDNA replication intermediates and it is unclear whether large ...
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: Phorbol 12-myristate 13-acetate (PMA) promotes skin cancer in rodents. The mutations found in murine tumors are similar to those found in human skin cancers, and PMA promotes proliferation of human skin cells. PMA treatment of human keratinocytes increases the synthesis of APOBEC3A, an enzyme that converts cytosines in single-stranded DNA to uracil, and mutations in a variety of human cancers are attributed to APOBEC3A or APOBEC3B expression. We tested here the possibility that induction of AP...
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#1Daniel J. Salamango (UMN: University of Minnesota)H-Index: 4
#2Jennifer L. McCann (UMN: University of Minnesota)H-Index: 5
Last. Reuben S. HarrisH-Index: 59
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Abstract The APOBEC3 family of cytosine deaminases catalyzes the conversion of cytosines-to-uracils in single-stranded DNA. Traditionally, these enzymes are associated with antiviral immunity and restriction of DNA-based pathogens. However, a role for these enzymes in tumor evolution and metastatic disease has also become evident. The primary APOBEC3 candidate in cancer mutagenesis is APOBEC3B (A3B) for three reasons: (1) A3B mRNA is upregulated in several different cancers, (2) A3B expression a...
8 CitationsSource
#1Shixiang Wang (CAS: Chinese Academy of Sciences)H-Index: 2
#2Mingming Jia (CAS: Chinese Academy of Sciences)H-Index: 1
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Non-small cell lung cancer (NSCLC) is known to carry heavy mutation load. Besides smoking, cytidine deaminase APOBEC3B plays a key role in the mutation process of NSCLC. APOBEC3B is also reported to be upregulated and predicts bad prognosis in NSCLC. However, targeting APOBEC3B high NSCLC is still a big challenge. Here we show that APOBEC3B upregulation is significantly associated with immune gene expression, and APOBEC3B expression positively correlates with known immunotherapy response biomark...
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#2Rachel RosenthalH-Index: 13
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Abstract The apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) mutational signature has only recently been detected in a multitude of cancers through next-generation sequencing. In contrast, APOBEC has been a focus of virology research for over a decade. Many lessons learnt regarding APOBEC within virology are likely to be applicable to cancer. In this review, we explore the parallels between the role of APOBEC enzymes in HIV and cancer evolution. We discuss data supporti...
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#1Matthew C. JarvisH-Index: 4
#2Diako EbrahimiH-Index: 13
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Background: Multiple endogenous and exogenous sources of DNA damage contribute to the overall mutation burden in cancer, with distinct and overlapping combinations contributing to each cancer type. Many mutation sources result in characteristic mutation signatures, which can be deduced from tumor genomic DNA sequences. Examples include spontaneous hydrolytic deamination of methyl-cytosine bases in CG motifs (AGEING signature) and C-to-T and C-to-G mutations in 5'-TC(A/T) motifs (APOBEC signature...
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#1Takeyuki Kono (NU: Northwestern University)
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Abstract The mechanisms regulating viral pathogenesis of human papillomavirus (HPV) associated oropharyngeal squamous cell cancers (OPSCC) are not well understood. In the cervix, activation of DNA damage repair pathways is critical for viral replication but little is known about their role in OPSCC. APOBEC factors have been shown to be increased in OPSCC but the significance of this is unclear. We therefore examined activation of DNA damage and APOBEC factors in HPV-induced OPSCC. Our studies sh...
Source
#1Emily K. LawH-Index: 11
#1Law Ek (UIC: University of Illinois at Chicago)
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The APOBEC3 family of antiviral DNA cytosine deaminases is implicated as the second largest source of mutation in cancer. This mutational process may be a causal driver or inconsequential passenger to the overall tumor phenotype. We show that human APOBEC3A expression in murine colon and liver tissues increases tumorigenesis. All other APOBEC3 family members including APOBEC3B did not as strongly promote liver tumor formation. DNA sequences from APOBEC3A-expressing animals display hallmark APOBE...
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