Activation of the B-cell surface receptor CD40 induces A20, a novel zinc finger protein that inhibits apoptosis.
CD40 activation is critical for B-cell function, leading to activation and expression of cell surface markers, proliferation, immunoglobulin class switching and inhibition of programmed cell death (PCD). Germinal center B-cells, for example, can be prevented from undergoing PCD by CD40 activation. The mechanism by which PCD is inhibited has been an enigma. A potential role for A20, a novel zinc finger protein, in inhibiting B-cell apoptosis was suggested by our previous finding that it is induced by the Epstein-Barr virus LMP-1 gene product, a potent cell death inhibitor. We now show that CD40 activation induces A20 and that expression of A20 renders B-cell lines resistant to PCD. Additionally, we show that CD40 activation of A20 expression is mediated by inducible binding of NF-kappa B complexes to the A20 promoter and provide evidence for a critical role for Thr234 (in the CD40 cytoplasmic domain) in activating NF-kappa B.
Sarma
V
V
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Lin
Z
Z
Clark
L
L
Rust
B M
BM
Tewari
M
M
Noelle
R J
RJ
Dixit
V M
VM
D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens; D002460:Cell Line; D005786:Gene Expression Regulation; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins; D015398:Signal Transduction; D016335:Zinc Fingers / Q000502:physiology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D016328:NF-kappa B; D011506:Proteins