Proteasomal degradation restricts the nuclear lifespan of AID

Balancing AID and DNA repair during somatic hypermutation

“…AID, Msh2 and Msh6 are expressed throughout the cell cycle [32][33][34]. In non-B cells, expression of Ung2 (the nuclear isoform of Ung) is cell-cycle regulated, with expression increasing sharply at the G1-S phase transition, reaching its peak in S phase, and gradually declining to undetectable levels at the end of S phase [35].…”

Insights into the B cell specific process of immunoglobulin class switch recombination

“…2). The half-life of AID is shorter in the nucleus than in the cytoplasm [77]. Polyubiquitinated nuclear AID has been detected in the presence of proteasome inhibitor, providing evidence for ubiquitination of AID as a posttranslational modification influencing its stability [77].…”

“…The half-life of AID is shorter in the nucleus than in the cytoplasm [77]. Polyubiquitinated nuclear AID has been detected in the presence of proteasome inhibitor, providing evidence for ubiquitination of AID as a posttranslational modification influencing its stability [77]. However, regulation of AID expression level starts already at the RNA level as two microRNAs: miR-155 [78,79] and miR-181b [80], has been demonstrated to target AID RNA.…”

Class-Switch Recombination Defects

“…It is probable that AID shuttles between the cytoplasm and the nucleus, where it is rapidly degraded by ubiquitination. 82 Activation-induced cytidine deaminase has an N-terminal nuclear localization signal (the role of which is still subject to debate 83 ) and a C-terminal nuclear export signal (NES, which plays a role in both nuclear shuttling and CSR specifically 84À87 ). Indeed, SHM appears to be normal and CSR is absent in a few patients carrying C-terminal mutations located upstream of the NES.…”