Analysis of mouse teeth hyperplasia and gut tissue enlargement by mutation of transcription factor Bcl11b

Bcl 11b/BCL 11B是一种C_2H_2锌指转录因子，具有单倍不足肿瘤抑制作用。人类直系同源物BCL 11 B的突变和缺失已在人类T细胞急性淋巴细胞白血病（T-ALL）和小鼠胸腺淋巴瘤模型中鉴定。我们已经研究了BCL 11 B是否直接影响p^53信号通路，包括HDM 2（一种降解p^53的泛素连接酶）。这是因为p^53通路调节细胞增殖和对DNA损伤的反应以维持基因组完整性。我们已经通过ChIP（染色质免疫沉淀）测定获得了BCL 11B与人HDM 2-P2启动子结合并以p^53依赖性方式抑制HDM 2表达的结果。这些数据表明BCL 11B影响p53-HDM 2反馈环的活性。这可能是T-ALL白血病转化和Bcl 11b S826 G/KO小鼠门齿发育障碍及肠腺扩大的机制之一。

Bcl11b/BCL11B is a C_2H_2 zinc finger transcription factor that acts as a haploinsufficient tumor suppressor. Mutations and deletion in the human orthologue BCL11B have been identified in human T-cell acute lymphoblastic leukemia (T-ALL) and a mouse model of thymic lymphomas. We have examined whether or not BCL11B directly affects the p^53 signaling pathway including HDM2, an ubiquitin ligase for p^53 degradation. This is because that the p^53 pathway regulates cell proliferation and the response to DNA damages to maintain genome integrity. We have obtained the results that BCL11B binds to human HDM2-P2 promoter by ChIP (chromatin immuno-precipitation) assay and inhibits HDM2 expression in a p^53-dependent manner. These date suggest that BCL11B affects the activity of the p53-HDM2 feedback loop. This may be a mechanism for the leukemic transformation in T-ALL and for the impairment of incisor development and the enlargement of intestine crypts in Bcl11b S826G/KO mouse.