title: Homeostatic defects in B cells deficient in the E3 ubiquitin ligase ARF-BP1 are restored by enhanced expression of MYC.
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.
authors.affiliation: Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States. Electronic address: cqi@niaid.nih.gov.
authors.forename: Chen-Feng
authors.initials: CF
authors.lastname: Qi
authors.forename: Ruihua
authors.initials: R
authors.lastname: Zhang
authors.forename: Jiafang
authors.initials: J
authors.lastname: Sun
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Li
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Shin
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Wang
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Kovalchuk
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sakai
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
authors.forename: Ning
authors.initials: N
authors.lastname: Kon
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000502:physiology; D016259:Genes, myc / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology; D006706:Homeostasis / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014162:Transfection; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D025521:Tumor Suppressor Proteins; C502831:Huwe1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: ARF-BP1; B cell development; MYC; p53