Regulation of VEGI by Soluble Death Receptor 3

可溶性死亡受体 3 对 VEGI 的调节

基本信息

批准号：
7152518
负责人：
Sam Grimaldo
金额：
$ 3.58万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-01-01 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7152518
关键词：
Activated Lymphocyte Acute Adaptor Signaling Protein Adult Affect Alternative Splicing Amino Acid Sequence Amino Acids Antibiotics Antibodies Apoptosis Attention Be++ element Beryllium Binding Biological Assay Biology Bos taurus Breast Cancer Cell Cancer Biology Caspase Cattle Cell Line Cell Surface Receptors Cell surface Cells Cessation of life Class Clinical Trials Conditioned Culture Media Culture Media Cultured Cells Cysteine-Rich Domain Death Domain Dimethyl Sulfoxide Dose Down-Regulation Endothelial Cells Enzyme-Linked Immunosorbent Assay Exons Family Family member Gene Expression Genes Growth Homeostasis Hour Immune Introns Lead Length Ligand Binding Ligands Lymphocyte MCF7 cell Malignant Neoplasms Mediating Membrane Membrane Proteins Methods Molecular Weight Mus Myelogenous NF-kappa B Neoplasms in Vascular Tissue Normal tissue morphology Northern Blotting Nuclear Nuclear Extract Pathway interactions Penicillins Peptide Signal Sequences Peripheral Blood Lymphocyte Pharmaceutical Preparations Procedures Production Property Protein Isoforms Proteins Purpose Recombinants Recruitment Activity Regulation Research Proposals Role Serum Signal Transduction Spleen Streptomycin T-Lymphocyte TNF Receptor-Associated Death Domain Protein TNFRSF1A gene TNFSF10 gene TNFSF6 gene TRADD gene TRAIL receptor 3 TRAMP protein Testing Therapeutic Thinking Thymus Gland Time Transmembrane Domain Tumor Angiogenesis Tumor Necrosis Factor Receptor Tumor Necrosis Factor Superfamily Ligands Tumor Necrosis Factor-alpha Tumor Necrosis Factors Tumor necrosis factor receptor 11b Up-Regulation Variant Western Blotting autocrine cancer cell cancer therapy caspase-3 cell transformation cell type cytokine cytotoxicity decoy receptor 3 density extracellular genetic regulatory protein human TNF protein human TNFSF15 protein inhibitor/antagonist leukemia member novel p65 polyclonal antibody prevent receptor receptor binding response success transcription factor tumor tumor growth

项目摘要

Alternate splicing of death receptor 3 (DR3) results in 8 soluble receptors . The hypothesis is that soluble DR3 (sDR3)variants are able to sequester its cognate ligand ,VEGI. This will be a novel mechanism of regulating VEGI activity. VEGI has anti-cancer activity and overexpresion of sDR3 may be mechanism of avoiding the anti-angiogenic properties of VEGI. Leukemia cells have the ability to switch there soluble DR3 isoforms to the full length isoform and the role of VEGI is unkown in these cells. If it is found that VEGI can induce apoptosis in leukemia cells after isform switching this will be provide new therapuetic approach for the use of VEGI in treatment of leukemia. Aim 1. Determine if recombinant sDR3 can inhibit VEGI activity in endothelial cells. Endothelial cells will be co-treated with recombinant sDR3 and recombinant VEGI in order to show that sDR3 can inhibit VEGI activation of NF-kb and caspase-3. Aim 2. Determine if isoform switching in leukemia cells results in an increase in VEGI activity. Leukemia cells will be induced to switch from their soluble DR3 variants to the membrane bound variant in order to show an increase in VEGI activation of NF-kb and caspase-3.

死亡受体3（DR3）的替代剪接会导致8个可溶性受体。假设是可溶 DR3（SDR3）变体能够隔离其同源配体Vegi。这将是一种新颖的机制调节VEGI活性。 VEGI具有抗癌活性，SDR3的过度主张可能是避免VEGI的抗血管生成特性。白血病细胞有能力切换那里可溶性DR3 全长同工型的同工型，在这些细胞中，Vegi的作用是不镇定的。如果发现Vegi可以在ISFORM切换后诱导白血病细胞中的凋亡，这将是新的治疗方法 VEGI治疗白血病。 AIM 1。确定重组SDR3是否可以抑制内皮细胞中的VEGI活性。内皮细胞将是与重组SDR3和重组VEGI共同治疗，以证明SDR3可以抑制VEGI NF-KB和caspase-3的激活。 AIM 2。确定白血病细胞中的同工型是否会导致 VEGI活性的增加。白血病细胞将被诱导从其可溶性DR3变体切换到膜结合变体以显示NF-KB和caspase-3的VEGI激活增加。