Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 44, Issue 7, Pages 2175-2187Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201343853
Keywords
Activation-induced deaminase (AID); Alternative splicing; Chronic lymphocytic leukemia (CLL)
Categories
Funding
- Austrian science fund FWF [P24619, SFB021, T516-B13]
- Klinische Malignom und Zytokinforschung Salzburg-Innsbruck GmbH
- province of Salzburg
- Austrian Science Fund (FWF) [T 516, P 24619] Funding Source: researchfish
- Austrian Science Fund (FWF) [P24619, T516] Funding Source: Austrian Science Fund (FWF)
Ask authors/readers for more resources
Activation-induced deaminase (AID) is a DNA-mutating enzyme that mediates class-switch recombination as well as somatic hypermutation of antibody genes in B cells. Due to off-target activity, AID is implicated in lymphoma development by introducing genome-wide DNA damage and initiating chromosomal translocations such as c-myc/IgH. Several alternative splice transcripts of AID have been reported in activated B cells as well as malignant B cells such as chronic lymphocytic leukemia (CLL). As most commercially available antibodies fail to recognize alternative splice variants, their abundance in vivo, and hence their biological significance, has not been determined. In this study, we assessed the protein levels of AID splice isoforms by introducing an AID splice reporter construct into cell lines and primary CLL cells from patients as well as from WT and TCL1(tg) C57BL/6 mice (where TCL1 is T-cell leukemia/lymphoma 1). The splice construct is 5'-fused to a GFP-tag, which is preserved in all splice isoforms and allows detection of translated protein. Summarizing, we show a thorough quantification of alternatively spliced AID transcripts and demonstrate that the corresponding protein abundances, especially those of splice variants AID-ivs3 and AID-Delta E4, are not stoichiometrically equivalent. Our data suggest that enhanced proteasomal degradation of low-abundance proteins might be causative for this discrepancy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available