Endogenous APOBEC3A DNA cytosine deaminase is cytoplasmic and nongenotoxic

Allison M. Land, Emily K. Law, Michael A. Carpenter, Lela Lackey, William L. Brown, Reuben S. Harris

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APOBEC3A (A3A) is a myeloid lineage-specific DNA cytosine deaminase with a role in innate immunity to foreign DNA. Previous studies have shown that heterologously expressed A3A is genotoxic, suggesting that monocytes may have a mechanism to regulate this enzyme. Indeed, we observed no significant cytotoxicity when interferon was used to induce the expression of endogenous A3A in CD14+-enriched primary cells or the monocytic cell line THP-1. In contrast, doxycycline-induced A3A in HEK293 cells caused major cytotoxicity at protein levels lower than those observed when CD14+ cells were stimulated with interferon. Immunofluorescent microscopy of interferon- stimulated CD14+ and THP-1 cells revealed that endogenous A3A is cytoplasmic, in stark contrast to stably or transiently transfected A3A, which has a cell-wide localization. A3A constructs engineered to be cytoplasmic are also nontoxic in HEK293 cells. These data combine to suggest that monocytic cells use a cytoplasmic retention mechanism to control A3A and avert genotoxicity during innate immune responses.

Original languageEnglish (US)
Pages (from-to)17253-17260
Number of pages8
JournalJournal of Biological Chemistry
Issue number24
StatePublished - Jun 14 2013

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