B LYMPHOCYTE INDUCED MATURATION PROTEIN

BLIMP-1(B淋巴细胞诱导成熟因子)首次被鉴定为 B细胞发育的主要调节者。这种锌指蛋白 在B细胞分化时被诱导，并足以驱动 淋巴瘤细胞系BCL1采用终末分化表型。这个 Pi的研究小组最近发现Blimp-1抑制c-myc基因 在B细胞中转录。因为c-Myc是细胞周期所必需的 进展，也是已知的阻止终末分化，它 C-Myc基因会被一种蛋白质抑制是有道理的 触发末端分化。此外，PI还提供了 初步数据显示Blimp-1的诱导并不局限于 B细胞也发生在终末分化的两个 早幼粒细胞系。此外，几个正常组织， 包括心脏和大脑，都有稳定水平的Blimp-1mRNA 与在脾中发现的相似。综合起来看，这些数据表明 BLIMP-1可能在多种细胞的终末分化中发挥作用 血统。 作为c-myc基因的抑制子，Blimp-1可作为肿瘤发挥作用 抑制者，因为c-Myc水平升高已知扮演着一种随意的 在许多肿瘤的致癌过程中起重要作用。Blimp-1基因位于 人类染色体6q21-22。有趣的是，淋巴细胞亚群， 乳腺癌、黑色素瘤和其他肿瘤在这个基因中有非随机的缺失 6号染色体的区域，表明存在肿瘤抑制基因。 研究人员提出了一项关于生物角色的分析 Blimp-1在终末分化中的作用，并可能作为一种肿瘤 抑制者。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 终末分化的培养细胞模型。她还将使用 灵敏的原位杂交法测定正常人 Blimp-1基因在胚胎发育过程中的表达 成人纸巾。Blimp-1可能的肿瘤抑制活性将 通过诱导该蛋白在多种细胞中异位表达进行测试 肿瘤线条。她还建议对生物化学进行系统分析。 确定Blimp-1如何抑制转录及其作用的机制 是在末端分化过程中被诱导的。私家侦探的实验室有 丰富的转录调控和B细胞研究经验 发展。这个项目汇集了许多方面的知识 调查员之前的工作，并专注于一个耐人寻味的 一种潜在的关键蛋白质，直到 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.