Phosphorylation directly regulates the intrinsic DNA cytidine deaminase activity of activation-induced deaminase and APOBEC3G protein

Zachary L. Demorest, Ming Li, Reuben S. Harris

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The beneficial effects ofDNAcytidine deamination by activation-induced deaminase (AID; antibody gene diversification) and APOBEC3G (retrovirus restriction) are tempered by probable contributions to carcinogenesis. Multiple regulatory mechanisms serve to minimize this detrimental outcome. Here, we show that phosphorylation of a conserved threonine attenuates the intrinsic activity of activation-induced deaminase (Thr-27) and APOBEC3G (Thr-218). Phospho-null alanine mutants maintain intrinsic DNA deaminase activity, whereas phosphomimetic glutamate mutants are inactive. The phospho-mimetic variants fail to mediate isotype switching in activated mouse splenic B lymphocytes or suppress HIV-1 replication in human T cells. Our data combine to suggest a model in which this critical threonine acts as a phospho-switch that fine-tunes the adaptive and innate immune responses and helps protect mammalian genomic DNA from procarcinogenic lesions.

Original languageEnglish (US)
Pages (from-to)26568-26575
Number of pages8
JournalJournal of Biological Chemistry
Volume286
Issue number30
DOIs
StatePublished - Jul 29 2011

Fingerprint Dive into the research topics of 'Phosphorylation directly regulates the intrinsic DNA cytidine deaminase activity of activation-induced deaminase and APOBEC3G protein'. Together they form a unique fingerprint.

  • Cite this