APOBEC Enzymes as Targets for Virus and Cancer Therapy

Margaret E. Olson, Reuben Harris, Daniel A Harki

Research output: Contribution to journalReview article

  • 6 Citations

Abstract

Human DNA cytosine-to-uracil deaminases catalyze mutations in both pathogen and cellular genomes. APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H restrict human immunodeficiency virus 1 (HIV-1) infection in cells deficient in the viral infectivity factor (Vif), and have the potential to catalyze sublethal levels of mutation in viral genomes in Vif-proficient cells. At least two APOBEC3 enzymes, and in particular APOBEC3B, are sources of somatic mutagenesis in cancer cells that drive tumor evolution and may manifest clinically as recurrence, metastasis, and/or therapy resistance. Consequently, APOBEC3 enzymes are tantalizing targets for developing chemical probes and therapeutic molecules to harness mutational processes in human disease. This review highlights recent efforts to chemically manipulate APOBEC3 activities. APOBECs are single-stranded DNA cytosine-to-uracil deaminases that perform essential roles in innate immunity by restricting foreign DNA; however, their aberrant activities can drive mutagenesis of virus and cancer genomes. Here, Olson et al. review chemical approaches to harness APOBEC mutagenesis as a new strategy to control genome evolution in human disease.

LanguageEnglish (US)
Pages36-49
Number of pages14
JournalCell Chemical Biology
Volume25
Issue number1
DOIs
StatePublished - Jan 18 2018

Fingerprint

Viruses
Mutagenesis
Uracil
Genes
Cytosine
Genome
Enzymes
Neoplasms
Mutation
Viral Genome
Single-Stranded DNA
DNA
Virus Diseases
Innate Immunity
HIV-1
Pathogens
Therapeutics
Neoplasm Metastasis
Tumors
Recurrence

Keywords

  • APOBEC
  • cancer
  • chemical probes
  • cytosine-to-uracil
  • mutation
  • virus

Cite this

APOBEC Enzymes as Targets for Virus and Cancer Therapy. / Olson, Margaret E.; Harris, Reuben; Harki, Daniel A.

In: Cell Chemical Biology, Vol. 25, No. 1, 18.01.2018, p. 36-49.

Research output: Contribution to journalReview article

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