Homeostatic defects in B cells deficient in the E3 ubiquitin ligase ARF-BP1 are restored by enhanced expression of MYC

Leuk Res. 2013 Dec;37(12):1680-9. doi: 10.1016/j.leukres.2013.09.009. Epub 2013 Sep 20.

Abstract

The E3 ligase ARF-BP1 governs the balance of life and death decisions by directing the degradation of p53 and enhancing the transcriptional activity of MYC. We find B cells selectively deficient in ARF-BP1 have many defects in developing and mature B cells associated with increased expression of p53 and reduced expression of Myc. Overexpression of Myc results in suppression of p53 and complete reversal of defects induced by ARF-BP1 deficiency. These findings indicate that the dynamic balance between MYC and p53 required for normal B cell maturation and function is finely tuned and critically dependent on the activities of ARF-BP1.

Keywords: ARF-BP1; B cell development; MYC; p53.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Gene Expression / physiology
  • Genes, myc / physiology*
  • Genes, p53 / physiology
  • Homeostasis / genetics*
  • Homeostasis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Transfection
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases / genetics*
  • Up-Regulation / physiology

Substances

  • Tumor Suppressor Proteins
  • Huwe1 protein, mouse
  • Ubiquitin-Protein Ligases