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APOBEC Enzymes as Targets for Virus and Cancer Therapy

Margaret E Olson1, Reuben S Harris2, Daniel A Harki3

  • 1Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.

Cell Chemical Biology
|November 21, 2017
PubMed

Insights

APOBEC3 enzymes cause mutations in DNA, impacting infections and cancer. Chemical manipulation of these enzymes offers potential therapeutic strategies for human diseases by controlling these mutational processes.

Area of Science:

  • Biochemistry
  • Genetics
  • Molecular Biology

Background:

  • Human DNA cytosine-to-uracil deaminases, including APOBEC3 enzymes, are implicated in genome mutagenesis.
  • APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H restrict human immunodeficiency virus 1 (HIV-1) infection.
  • APOBEC3B is a significant source of somatic mutagenesis in cancer, driving tumor evolution and clinical outcomes.

Purpose of the Study:

  • To review recent advancements in the chemical manipulation of APOBEC3 enzyme activities.
  • To explore the therapeutic potential of targeting APOBEC3 enzymes in human diseases.

Main Methods:

  • This review synthesizes recent research on chemical modulation of APOBEC3 enzymes.
  • Focuses on strategies to harness or inhibit APOBEC3-driven mutagenesis.

Main Results:

  • APOBEC3 enzymes can mutate pathogen and cellular genomes.
  • These enzymes play a role in HIV-1 restriction and cancer mutagenesis.
  • Chemical approaches are being developed to control APOBEC3 activity.

Conclusions:

  • APOBEC3 enzymes are critical players in viral restriction and cancer development.
  • Targeting APOBEC3 enzymes with chemical probes and therapeutics holds promise for treating diseases.
  • Further research into chemical manipulation of APOBEC3s is essential for therapeutic development.
Keywords:
APOBECcancerchemical probescytosine-to-uracilmutationvirus

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