PSF Regulates the Porcine P450scc IFGRE

PSF 监管猪 P450scc IFGRE

• 批准号: 7150594
• 负责人: Randall J Urban
• 金额: $ 26.39万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7150594
• 关键词: Affect; Aromatase; Binding; Cell Line; Cell membrane; Cells; Cholesterol; Complex; Cytochrome P450; Data; Disease; Enzymes; Family suidae; Future; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Gonadotropins; Hormonal; Hormones; Insulin-Like Growth Factor I; Knowledge; Lead; Mediating; Mus; Nuclear; Nucleic Acid Regulatory Sequences; Ovarian; Ovary; PTB-associated splicing factor; Pathway interactions; Phosphorylation; Phosphorylation Site; Phosphotransferases; Polycystic Ovary Syndrome; Polymerase; Polypyrimidine Tract-Binding Protein; Protein Overexpression; Publications; RNA; Rate; Regulation; Repression; Reproductive Endocrinology; Response Elements; Retrotransposon; Side; Signal Pathway; Signal Transduction; Steroid biosynthesis; Threonine; Validation; Work; atypical protein kinase C; concept; granulosa cell; novel; prevent; protein kinase C iota; protein protein interaction; reproductive; research study; tool; transcription factor

DESCRIPTION (provided by applicant): Our work focuses on IGF-I regulation of gene expression for P-450 cholesterol side-chain cleavage (P450scc), the rate-limiting enzyme in the steroidogenic pathway. We identified an IGF-I response element (IGFRE) of the porcine P450scc gene that binds Sp1(stimulator) and polypyrimidine tract-binding protein (PTB)-associated splicing factor (PSF, repressor). In this proposal we will investigate mechanisms of PSF regulation of IGFRE activity. Studies will be conducted in a stable porcine granulosa cell line, the JC-410 cells. We hypothesize that PSF repression of the IGFRE involves a mechanism that prevents IGF-I-stimulated phosphorylation of Sp1. In specific aim 1 we will determine IGF-I-mediated Sp1 phosphorylation sites having already demonstrated that IGF-I stimulates phosphorylation of threonine 739 on Sp1, a known erk 1/2 phosphorylation site. In specific aim 2 we will investigate the erk 1/2 signaling pathway as at least a partial mechanism for regulating IGF-I stimulation of the IGFRE through Sp1 phosphorylation. Finally, we will investigate protein kinase C (PKC) iota as a modulator of PSF-Sp1 interactions regulating the IGFRE (specific aim 3). We will determine the fundamental mechanisms whereby IGF-I controls P450scc gene expression through interactions of Sp1, PSF, and PKC iota. This knowledge will increase our understanding and provide the basic background for novel concepts on hormonal control of ovarian steroidogenesis.

描述（由申请人提供）：我们的工作重点是IGF-I调控P-450胆固醇侧链切割（P450scc）的基因表达，P450scc是类固醇生成途径中的限速酶。我们在猪P450scc基因中发现了一个IGF-I反应元件（IGFRE），该元件结合Sp1（刺激因子）和多嘧啶束结合蛋白（PTB）相关剪接因子（PSF，阻遏因子）。