Authors: | Basu, U.; Franklin, A.; Schwer, B.; Cheng, H. L.; Chaudhuri, J.; Alt, F. W. |
Article Title: | Regulation of activation-induced cytidine deaminase DNA deamination activity in B-cells by Ser38 phosphorylation |
Abstract: | Human and mouse Ig genes are diversified in mature B-cells by distinct processes known as Ig heavy-chain CSR (class switch recombination) and Ig variable-region exon SHM (somatic hypermutation). These DNA-modification processes are initiated by AID (activation-induced cytidine deaminase), a DNA cytidine deaminase predominantly expressed in activated B-cells. AID is post-transcriptionally regulated via multiple mechanisms, including microRNA regulation, nucleocytoplasmic shuttling, ubiquitination and phosphorylation. Among these regulatory processes, AID phosphorylation at Ser<sup>38</sup> has been a focus of particularly intense study and debate. In the present paper, we discuss recent biochemical and mouse genetic studies that begin to elucidate the functional significance of AID Ser<sup>38</sup> phosphorylation in the context of the evolution of this mode of AID regulation and the potential roles that it may play in activated B-cells during a normal immune response. © The Authors Journal compilation © 2009 Biochemical Society. |
Keywords: | protein expression; protein phosphorylation; exon; mutation; nonhuman; conference paper; mouse mutant; animals; mice; microrna; serine; genetic variability; evolution; enzyme activity; phosphorylation; b lymphocyte; b-lymphocytes; evolution, molecular; molecular mechanics; lymphocyte activation; activation-induced cytidine deaminase (aid); class switch recombination; somatic hypermutation; activation induced cytidine deaminase; dna; double stranded dna; immunoglobulin heavy chain; cellular immunity; deamination; dna modification; enzyme phosphorylation; enzyme regulation; gene rearrangement; genetic recombination; immune response; immunoglobulin gene; immunoglobulin variable region; molecular evolution; nucleocytoplasmic transport; protein processing; regulatory mechanism; transcription regulation; ubiquitination; amino acid sequence; conserved sequence; cytidine deaminase; immunoglobulin heavy chains; molecular sequence data; protein processing, post-translational; sequence homology, amino acid; species specificity |
Journal Title: | Biochemical Society Transactions |
Volume: | 37 |
Issue: | 3 |
ISSN: | 0300-5127 |
Publisher: | Portland Press Ltd |
Date Published: | 2009-06-01 |
Start Page: | 561 |
End Page: | 568 |
Language: | English |
DOI: | 10.1042/bst0370561 |
PUBMED: | 19442251 |
PROVIDER: | scopus |
PMCID: | PMC3540414 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: BCSTB" - "Source: Scopus" |