FUNCTION AND REGULATION OF C/EBP PROTEINS

C/EBP 蛋白的功能和调节

• 批准号: 6419907
• 负责人: PETER JOHNSON
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6419907
• 关键词: cell differentiation; cell growth regulation; enhancer binding protein; gene induction /repression; inflammation; laboratory mouse; neoplasm /cancer genetics; protein structure function

Changes in gene expression underlie many fundamental cellular processes, including growth, differentiation, and tumorigenesis. The research in our laboratory focuses on the CCAAT/enhancer binding protein (C/EBP) family of transcription factors, which belong to the basic-leucine zipper (bZIP) class of DNA-binding proteins. The C/EBP proteins (C/EBPa, C/EBPb, C/EBPd, C/EBPe, and C/EBPg) recognize a common DNA sequence, exhibit similar leucine zipper dimerization specificities and, with the exception of C/EBPg, function mainly as transcriptional activators. Our research is aimed at elucidating the roles of C/EBP proteins in regulating cell growth and differentiation, as well as cellular responses to stress and inflammation. We are also interested in understanding the mechanisms that control the activity of C/EBP proteins in response to specific signal transduction pathways. Other projects involve determining the dimeric status of C/EBP proteins in cells and investigating how changes in dimerization partners affect their transcriptional activity. We are using cell culture systems as well as mouse models (targeted mutations) to address these questions. Recently, we have begun to investigate the involvement of C/EBP proteins in oncogenic transformation and tumorigenesis. C/EBPs can cause cell growth arrest when expressed in dividing cells, but have also been reported to promote cell proliferation in response to specific growth signals. These observations suggest that C/EBP proteins might function as tumor suppressors and/or as pro-oncogenes, depending on the C/EBP family member and the cell type involved. Studies using mice carrying null mutations in specific C/EBP genes indicate that these proteins are involved as both positive and negative regulators of tumorigenesis.

基因表达的变化是许多基本细胞过程的基础，包括生长，分化和肿瘤发生。我们实验室中的研究集中于转录因子的CCAAT/增强子结合蛋白（C/EBP）家族，这些家族属于碱性亮氨酸拉链（BZIP）类DNA结合蛋白的类别。 C/EBP蛋白（C/EBPA，C/EBPB，C/EBPD，C/EBPE和C/EBPG）识别一个共同的DNA序列，表现出相似的亮氨酸拉链二聚体特异性，并且除C/EBPG外，主要是C/EBPG（主要用作转录激活器）。我们的研究旨在阐明C/EBP蛋白在调节细胞生长和分化以及对压力和炎症的细胞反应中的作用。 我们还有兴趣了解控制C/EBP蛋白活性的机制，以响应特定的信号转导途径。 其他项目涉及确定细胞中C/EBP蛋白的二聚体状态，并研究二聚伴侣的变化如何影响其转录活性。我们正在使用细胞培养系统以及小鼠模型（靶向突变）来解决这些问题。最近，我们开始研究C/EBP蛋白在致癌转化和肿瘤发生中的参与。 C/EBP在分裂细胞中表达时会导致细胞生长停滞，但也据报道以响应特定的生长信号促进细胞增殖。 这些观察结果表明，根据C/EBP家族成员以及所涉及的细胞类型，C/EBP蛋白可能充当肿瘤抑制剂和/或亲蛋白抑制剂。 使用在特定C/EBP基因中携带无效突变的小鼠的研究表明，这些蛋白质既是肿瘤发生的阳性和阴性调节剂。