Transcriptional regulation of APOBEC3G, a cytidine deaminase that hypermutates human immunodeficiency virus

Kristine M. Rose, Mariana Marin, Susan L. Kozak, David Kabat

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Abstract

Apolipoproiein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) is an antiretroviral deoxycytidine deaminase that lethally hypermutates human immunodeficiency virus type 1 (HIV-1) but is itself neutralized by the HIV-1-encoded viral infectivity factor. Accordingly, APOBEC3G occurs specifically in human T lymphocytic cell lines that contain this antiviral defense, including H9. Since the substrate specificities of related cytidine deaminases are strongly influenced by their intracellular quantities, we analyzed the factors that control APOBEC3G expression. The levels of APOBEC3G mRNA and protein were unaffected by treatment of proliferating H9 cells with interferons or tumor necrosis factor-α but were enhanced up to 20-fold by phorbol myristate acetate. This induction was mediated at the transcriptional level by a pathway that required activation of the protein kinase Cα/βI isozyme (PKC), mitogen-activated protein kinase kinase (MEK) 1 and 2, and extracellular signal-regulated kinase (ERK). Correspondingly, induction of APOBEC3G was blocked by multiple inhibitors that act at diverse steps of this pathway. The PKCα/βI/MEK/ERK pathway also controlled, basal levels of APOBEC3G mRNA and protein, which consequently declined when cells were treated with these inhibitors or arrested in the G0 state of the cell cycle by serum starvation. We conclude that expression of the antiviral APOBEC3G editing enzyme is dynamically controlled by the PKCα/βI/MEK/ERK protein kinase cascade in human T lymphocytes.

Original languageEnglish (US)
Pages (from-to)41744-41749
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number40
DOIs
Publication statusPublished - Oct 1 2004

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ASJC Scopus subject areas

  • Biochemistry

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