Activation of the B-cell Surface Receptor CD40 Induces A20, a Novel Zinc Finger Protein That Inhibits Apoptosis

J Biol Chem. 1995 May 26;270(21):12343-6. doi: 10.1074/jbc.270.21.12343.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / metabolism*
  • Antigens, Differentiation, B-Lymphocyte / metabolism*
  • Apoptosis / physiology*
  • B-Lymphocytes / physiology*
  • CD40 Antigens
  • Cell Line
  • Gene Expression Regulation*
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic
  • Protein Biosynthesis*
  • Proteins*
  • Signal Transduction
  • Zinc Fingers / physiology

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD40 Antigens
  • NF-kappa B
  • Proteins