B-ATF IN B CELL GROWTH, DEVELOPMENT AND MALIGNANCIES

B-ATF 在 B 细胞生长、发育和恶性肿瘤中的作用

• 批准号: 2872022
• 负责人: ELIZABETH J TAPAROWSKY
• 金额: $ 24.78万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-20 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2872022
• 关键词: B lymphocyte; Epstein Barr virus; cell growth regulation; gene expression; gene induction /repression; gene targeting; genetic promoter element; genetically modified animals; hematopoietic stem cells; in situ hybridization; laboratory mouse; leukemia; leukocyte activation /transformation; neoplastic growth; nucleoproteins; oncoproteins; protein structure function; transcription factor; viral carcinogenesis

DESCRIPTION: The functional characterization of tissue-specific transcription factors that regulate hematopoietic cell growth and lineage development will provide molecular targets for the design of strategies to manipulate the leukemic phenotype. B-ATF is a new basic leucine zipper (bZIP) protein that is expressed in a tissue-specific manner and is induced rapidly in human B cells following infection with Epstein-Barr virus (EBV) and the expression of the EBV-encoded transactivator protein, EBNA-2. B-ATF is a nuclear protein that heterodimerizes with members of the Jun family of oncoproteins to bind to AP-1 target DNA sites. In cultured cells engineered to overexpress B-ATF, Jun, and Fos, transcription of an AP-1 responsive reporter gene is repressed. This suggests that B-ATF functions as a negative regulator of AP-1, a transcription complex that normally is associated with the induction of cellular growth. Based on these observations, it remains unclear why EBNA-2, a viral latency gene product required for B cell immortalization and transformation, triggers the expression of B-ATF. To explore further the relationship between EBV and B-ATF, the cis-trans regulatory mechanisms responsible for enhanced expression of the human B-ATF gene by EBNA-2 will be investigated. To establish a functional role for B-ATF in B cells, experiments will be performed to assess the impact of B-ATF on the biochemical and biological function of the AP-1 transcription factor complex and on the activities of an additional B-ATF-interacting protein (BIP-13) that is expressed preferentially in human B cells. The requirement for spatial and temporal control of B-ATF expression in vivo will be investigated using in situ hybridization to fully characterize the B-ATF gene expression pattern in embryonic and adult mice. Transgenic technology will be used to establish if perturbation of B-ATF expression adversely impacts the development of the whole animal. The PI anticipates that these studies will elucidate the role of B-ATF in B cell growth and development and provide the information needed to assess the feasibility of using this new bZIP protein as a target in the management of B cell malignancies.

描述：组织特异性的功能表征