A BTB-ZF protein, ZNF131, is required for early B cell development
A BTB-ZF protein, ZNF131, is required for early B cell development
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DOI：
10.1016/j.bbrc.2018.05.044
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发表时间：
2018-06-22
影响因子：
3.1
通讯作者：
Miyatake, Shoichiro
中科院分区：
文献类型：
--
作者：
Iguchi, Tomohiro;Miyauchi, Emako;Miyatake, Shoichiro
BTB-ZF转录因子家族成员在淋巴细胞发育中起重要作用。在T细胞发育过程中，ZNF 131是一种BTB-ZF蛋白，对于双阴性（DN）到双阳性（DP）的转变至关重要，并且还参与细胞增殖。在此，我们报告了在mbl-Cre基因敲入小鼠的前原B细胞阶段敲除Znf 131导致前B细胞缺陷向前B细胞转变。ZNF 131被证明是有效的前B细胞增殖以及增殖的前B细胞中发生的免疫球蛋白重链基因重排所必需的。我们推测，低效的基因重排可能是由于细胞增殖的损失，因为细胞周期进程和免疫球蛋白基因重排，这将发生在一个相互排斥的方式，可能是相互关联或耦合，以避免发生基因组不稳定性。ZNF 131抑制Cdk抑制剂p21（ciP 1）和促凋亡因子Box和Puma（p53的靶点）的表达，分别促进细胞周期进展和抑制pro-B细胞不必要的凋亡。这些结果表明ZNF 131在协调B细胞分化和增殖中起重要作用。(C)2018爱思唯尔公司All rights reserved.
Members of the BTB-ZF transcription factor family play important roles in lymphocyte development. During T cell development, ZNF131, a BTB-ZF protein, is critical for the double-negative (DN) to double positive (DP) transition and is also involved in cell proliferation. Here, we report that knockout of Znf131 at the pre-pro-B cell stage in mbl-Cre knock-in mouse resulted in defect of pro-B to pre-B cell transition. ZNF131 was shown to be required for efficient pro-B cell proliferation as well as for immunoglobulin heavy chain gene rearrangement that occurs in the proliferating pro-B cells. We speculate that inefficient gene rearrangement may be due to loss of cell proliferation, since cell cycle progression and immunoglobulin gene rearrangement, which would occur in a mutually exclusive manner, may be interconnected or coupled to avoid occurrence of genomic instability. ZNF131 suppresses expression of Cdk inhibitor, p21(ciP1), and that of pro-apoptotic factors, Box and Puma, targets of p53, to facilitate cell cycle progression and suppress unnecessary apoptosis, respectively, of pro-B cells. There results demonstrate the essential roles of ZNF131 in coordinating the B cell differentiation and proliferation. (C) 2018 Elsevier Inc. All rights reserved.