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APOBEC3H Subcellular Localization Determinants Define Zipcode for Targeting HIV-1 for Restriction

Daniel J Salamango1,2,3, Jordan T Becker4,2,3, Jennifer L McCann4,2,3

  • 1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA dsalaman@umn.edu rsh@umn.edu.

Molecular and Cellular Biology
|September 19, 2018
PubMed

Insights

APOBEC3H enzymes are DNA mutators found in the cytoplasm and nucleolus. Specific structural elements control their location and viral restriction, influencing cancer and HIV-1.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • APOBEC enzymes are DNA cytosine deaminases with roles in antiviral defense and cancer mutagenesis.
  • APOBEC3H, a key member, is implicated in cancer but its cellular regulation remains poorly understood.

Purpose of the Study:

  • To investigate the subcellular localization and regulatory mechanisms of APOBEC3H.
  • To identify structural determinants governing APOBEC3H localization and function.

Main Methods:

  • Localization studies using native and fluorescently tagged APOBEC3H in various cell types.
  • Genetic, pharmacologic, and cell biological approaches to analyze retention and diffusion mechanisms.
  • Functional assays to assess the impact of APOBEC3H determinants on APOBEC3A and HIV-1 restriction.

Main Results:

  • APOBEC3H localizes to distinct cytoplasmic and nucleolar compartments.
  • Active retention mechanisms govern cytoplasmic and nucleolar localization, while nuclear transport is passive.
  • APOBEC3H structural determinants can redirect APOBEC3A and confer potent HIV-1 restriction.

Conclusions:

  • APOBEC3H possesses a "structural zipcode" dictating its subcellular localization.
  • This localization mechanism is crucial for selecting viral substrates and mediating restriction.
  • Understanding APOBEC3H regulation provides insights into cancer mutagenesis and antiviral strategies.
Keywords:
APOBEC3HDNA deaminationcancer mutagenesiscytoplasmic retentionnuclear importretrovirus restrictionsubcellular localization

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