APOBEC Enzymes as Targets for Virus and Cancer Therapy

Margaret E Olson; Reuben S Harris; Daniel A Harki

doi:10.1016/j.chembiol.2017.10.007

APOBEC Enzymes as Targets for Virus and Cancer Therapy

Cell Chem Biol. 2018 Jan 18;25(1):36-49. doi: 10.1016/j.chembiol.2017.10.007. Epub 2017 Nov 16.

Authors

Margaret E Olson¹, Reuben S Harris², Daniel A Harki³

Affiliations

¹ Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
² Howard Hughes Medical Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
³ Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: daharki@umn.edu.

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.

Keywords: APOBEC; cancer; chemical probes; cytosine-to-uracil; mutation; virus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

APOBEC Deaminases / antagonists & inhibitors*
APOBEC Deaminases / metabolism
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
HIV-1 / drug effects*
HIV-1 / enzymology
Humans
Neoplasms / drug therapy*
Neoplasms / enzymology

Substances

Anti-HIV Agents
Antineoplastic Agents
Enzyme Inhibitors
APOBEC Deaminases

Abstract

Publication types

MeSH terms

Substances

Grants and funding