Dataset Information


Amino-terminal phosphorylation of activation-induced cytidine deaminase suppresses c-myc/IgH translocation.

ABSTRACT: Activation-induced cytidine deaminase (AID) is a mutator enzyme that initiates class switch recombination and somatic hypermutation of immunoglobulin genes (Ig) in B lymphocytes. However, AID also produces off-target DNA damage, including mutations in oncogenes and double-stranded breaks that can serve as substrates for oncogenic chromosomal translocations. AID is strictly regulated by a number of mechanisms, including phosphorylation at serine 38 and threonine 140, which increase activity. Here we show that phosphorylation can also suppress AID activity in vivo. Serine 3 is a novel phospho-acceptor which, when mutated to alanine, leads to increased class switching and c-myc/IgH translocations without affecting AID levels or catalytic activity. Conversely, increasing AID phosphorylation specifically on serine 3 by interfering with serine/threonine protein phosphatase 2A (PP2A) leads to decreased class switching. We conclude that AID activity and its oncogenic potential can be downregulated by phosphorylation of serine 3 and that this process is controlled by PP2A.

SUBMITTER: Gazumyan A 

PROVIDER: S-EPMC3028632 | BioStudies | 2011-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC2571933 | BioStudies
1000-01-01 | S-EPMC5788578 | BioStudies
1000-01-01 | S-EPMC17932 | BioStudies
2009-01-01 | S-EPMC2745967 | BioStudies
1000-01-01 | S-EPMC1482658 | BioStudies
2012-01-01 | S-EPMC3571766 | BioStudies
2019-01-01 | S-EPMC6715587 | BioStudies
2018-01-01 | S-EPMC5823843 | BioStudies
2006-01-01 | S-EPMC4601098 | BioStudies
2017-01-01 | S-EPMC5717335 | BioStudies