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

• Published in: Leukemia research Vol. 37; no. 12; pp. 1680 - 1689
• Main Authors: Qi, Chen-Feng, Zhang, Ruihua, Sun, Jiafang, Li, Zhaoyang, Shin, Dong-Mi, Wang, Hongsheng, Kovalchuk, Alexander L, Sakai, Tomomi, Xiong, Huabao, Kon, Ning, Gu, Wei, Morse, Herbert C
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2013
• Subjects: Animals; ARF-BP1; B cell development; B-Lymphocytes - physiology; Cell Differentiation - genetics; Cell Differentiation - immunology; Gene Expression - physiology; Genes, myc - physiology; Genes, p53 - physiology; Hematology, Oncology and Palliative Medicine; Homeostasis - genetics; Homeostasis - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; MYC; p53; Transfection; Ubiquitin-Protein Ligases - genetics; Up-Regulation - physiology; ARF-BP1; B cell development; MYC; p53
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2013.09.009

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.