C/EBP BETA IN HEPATOCYTE GENE EXPRESSION & PROLIFERATION

肝细胞基因表达中的 C/EBP Beta

• 批准号: 6380824
• 负责人: MARIO CHOJKIER
• 金额: $ 29.74万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380824
• 关键词: DNA binding protein; albumins; athymic mouse; biological signal transduction; cachexia; cell differentiation; cell growth regulation; cell proliferation; clinical research; enhancer binding protein; fluorescence microscopy; gene expression; genetically modified animals; human subject; immunocytochemistry; in situ hybridization; laboratory mouse; liver cells; nitric oxide; oxidative stress; phosphorylation; site directed mutagenesis; tissue /cell culture; transcription factor; transfection /expression vector; transforming growth factors

DESCRIPTION: This renewal proposal focuses on the signal transduction pathways that modulate hepatocyte gene expression and proliferation through site-specific phosphorylations of C/EBP-beta. Preliminary results show that TGF-alpha and phorbol esters/PKC-alpha mediate their effects on hepatocyte proliferation, at least in part, through the activation of ribosomal S6-kinase and phosphorylation of C/EBP-beta on its activation domain. In addition, cachexia and TNF-alpha inhibit albumin transcription, at least in part, throug an oxidative stress/NO cascade resulting in the activation of stress-activated protein (SAP)- kinase and phosphorylation of C/EBP-beta on its basic domain, which abolishes the binding of C/EBP-beta to the albumin enhancer/promoter DNA sequence. The specific aims are 1) assess the role of phosphorylation on hepatocyte proliferation, 2) examine the modulation of hepatocyte proliferatio in C/EBP-beta mice, 3) examine the regulation of the cell cycle by C/EBP-beta in hepatocytes, 4) assess the role of oxidative stress and NO on C/EBP-beta phosphorylation and inhibition of albumin transcription induced by cachexia an TNF-alpha, 5) examine the modulation of albumin expression in C/EBP-beta transgenic mice, and 6) examine the mechanisms that induce decreased albumin expression in human cachexia.

描述：本更新建议侧重于信号转导