B LYMPHOCYTE INDUCED MATURATION PROTEIN

Blimp-1（B淋巴细胞诱导成熟因子）首先被鉴定为 是B细胞发育的主要调节器 这种锌指蛋白 在B细胞分化时被诱导，并且足以驱动 淋巴瘤细胞系BCL 1采用终末分化表型。 的 PI的研究小组最近发现Blimp-1抑制c-myc基因 在B细胞中的转录。 由于c-Myc是细胞周期所必需的， 进展，并且也已知阻断终末分化， c-Myc基因会被一种蛋白质抑制， 触发了终端分化。 此外，PI表示 初步数据显示，Blimp-1的诱导并不局限于 B细胞的终末分化， 早幼粒细胞系 另外，几种正常组织， 包括心脏和大脑，具有稳定的Blimp-1 mRNA水平， 与脾脏中发现的相似。 综合这些数据表明， Blimp-1可能在许多细胞的终末分化中起作用 血统 Blimp-1作为c-myc基因的阻遏物，可作为肿瘤的抑制剂， 由于已知c-Myc水平升高会导致 在许多肿瘤的发生中起作用。 blimp-1基因位于 人类染色体6 q21 -22。 有趣的是，淋巴细胞亚群， 乳腺癌、黑色素瘤和其他肿瘤在这一基因上有非随机缺失， 6号染色体区域，表明存在肿瘤抑制因子。 研究人员提出了一个生物学作用的分析， Blimp-1在终末分化中，可能作为肿瘤 抑制器。 Blimp-1在终端中作用的实验研究 分化将利用转基因小鼠和几个 用于终末分化的培养细胞模型。 她还将使用 敏感的原位杂交方法，以确定正常的 Blimp-1 mRNA在胚胎发育过程中的表达模式 成人组织 Blimp-1可能的肿瘤抑制活性将 通过在多种细胞中诱导蛋白质的异位表达来测试。 肿瘤线 她还提出了系统的生化分析， 机制来确定Blimp-1如何抑制转录，以及它如何 在终末分化过程中被诱导。 私家侦探的实验室 在转录调控和B细胞 发展 这个项目汇集了许多方面的 调查员以前的工作，并侧重于一个有趣的， 一种潜在的关键蛋白质，它一直没有受到太多的关注， 现在

Blimp-1(B lymphocyte induced maturation factor) was first identified as a master regulator of B-cell development. This zinc finger protein is induced upon B cell differentiation and is sufficient to drive the lymphoma line BCL1 to adopt a terminally differentiated phenotype. The PI's group has recently shown that Blimp-1 represses c-myc gene transcription in B cells. Since c-Myc is required for cell cycle progression and is also known to block terminal differentiation, it makes sense that the c-Myc gene would be repressed by a protein which triggers terminal differentiation. Furthermore, the PI presents preliminary data showing that induction of Blimp-1 is not restricted to B cells but also occurs upon terminal differentiation of two promyelocytic cell lines. In addition, several normal tissues, including heart and brain, have steady-state levels of Blimp-1 mRNA similar to that found in spleen. Taken together these data suggest that Blimp-1 may play a role in terminal differentiation of many cell lineages. As a repressor of the c-myc gene, Blimp-1 could function as a tumor suppressor since elevated levels of c-Myc are known to play a casual role in oncogenesis of many tumors. The blimp-1 gene is located on human chromosome 6q21-22. Interestingly, subsets of lymphocytic, breast, melanoma and other tumors have non-random deletions in this regions of chromosome 6, suggesting the presence of a tumor suppressor. The investigator proposes an analysis of the biological roles played by Blimp-1 in terminal differentiation and, possibly, as a tumor suppressor. The experiments on the role of Blimp-1 in terminal differentiation will take advantage of transgenic mice and several cultured cell models for terminal differentiation. She will also use sensitive in situ hybridization methods to determine the normal expression pattern of Blimp-1 mRNA during embryonic development and in adult tissues. The possible tumor suppressor activity of Blimp-1 will be tested by inducing ectopic expression of the protein in a variety of tumor lines. She also proposes systematic analyses of biochemical mechanisms to determine how Blimp-1 represses transcription and how it is induced during terminal differentiation. The PI's laboratory has extensive experience studying transcriptional regulation and B-cell development. This project draws together many facets of the investigator's previous work and focuses on an intriguing and potentially critical protein which has not received much attention until now.