Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
Leuk Res. 2013 Dec;37(12):1680-9. doi: 10.1016/j.leukres.2013.09.009. Epub 2013 Sep 20.
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.
E3 连接酶 ARF-BP1 通过指导 p53 的降解和增强 MYC 的转录活性来控制生死决定的平衡。我们发现 ARF-BP1 选择性缺乏的 B 细胞在发育和成熟 B 细胞中存在许多缺陷，这些缺陷与 p53 表达增加和 Myc 表达减少有关。Myc 的过表达导致 p53 抑制和 ARF-BP1 缺乏引起的缺陷完全逆转。这些发现表明，正常 B 细胞成熟和功能所需的 MYC 和 p53 之间的动态平衡是精细调节的，并且严重依赖于 ARF-BP1 的活性。
