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A Study of Biological Function of Basonuclin

碱性核蛋白的生物学功能研究

基本信息

批准号：
7911749
负责人：
GEORGE COTSARELIS
金额：
$ 39.6万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-10 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7911749
关键词：
Affect Area Arts Basal cell carcinoma Biochemical Biochemical Pathway Bioinformatics Biological Biological Assay Biological Process Biology Cell Adhesion Cell Differentiation process Cell Proliferation Cell physiology Cells Cloning Code Complex Cutaneous DNA DNA Polymerase I DNA Polymerase II DNA-Directed RNA Polymerase Data Defect Development Emergency Situation Epidermal Growth Factor Receptor Epidermis Epithelial Epithelium Equilibrium Exhibits Funding GLI Family Protein GLI2 gene Gene Expression Gene Targeting Genes Genetic Transcription Genomics Goals Hair Hair follicle structure Healed Homeostasis In Vitro Injury Knock-out Knockout Mice Knowledge Lead Light Link MAP Kinase Gene MAPK14 gene Maintenance Malignant Neoplasms Mediating Modeling Molecular Molecular Profiling Monitor Movement Mus Mutant Strains Mice Mutation Natural regeneration Neoplastic Cell Transformation Online Mendelian Inheritance In Man Pathway interactions Phenotype Process Proteins RNA Polymerase I Recombinant DNA Research Ribosomal RNA Role Signal Transduction Skin Skin Cancer Stem cells Stratified Epithelium Structure Techniques Testing Thick Time Tissues Transcript Transforming Growth Factor alpha Tumor Necrosis Factor-alpha Up-Regulation Variant Wound Healing Zinc Fingers base basonuclin beta catenin cancer cell cell type corneal epithelium healing human TNF protein in vivo inhibitor/antagonist keratinocyte mRNA Expression migration mouse model novel novel therapeutic intervention null mutation promoter rRNA Genes receptor repaired response restoration skin disorder skin regeneration smoothened signaling pathway stem cell biology tissue regeneration transcription factor tumorigenesis wound

项目摘要

Our long-term goal is to understand the role of the basonuclin gene in skin and hair follicle biology. Basonuclin (BNC1) is a zinc finger protein found in abundance in the keratinocytes of the epidermis and hair follicle. We believe that it coordinates activity of other genes through transcription factor activity. Our biochemical and bioinformatic studies show that BNC1 regulates transcription of genes in six different pathways. The BNC1 regulatory network is linked to pathways such as EGFR, p38 MAPK and TGFalpha. These genes control important cellular functions like proliferation, migration and differentiation. BNC1 is up-regulated in basal cell carcinoma (BCC). Our study of a Bnc1 knock out model suggests that it is required for hair follicle regeneration after hairplucking, and Bnc1-null mutation delays restoration of hair follicular stem cells after hairplucking. In this proposal, we will evaluate the role of Bnc-1 and Bnc-2 in skin regeneration, wound repair and hair follicle cycling. We will characterize how the Bnc1- null mutation affects hair regeneration, including determination of which cellular processes are affected by this mutation and what molecular perturbations are caused by Bnc1-null mutation. By examining Bnc-1 and Bnc-2 single and double knockout mice, we will assess the contribution of these genes to maintenance of epithelial stem cells in the bulge as well as the response of these cells to injury. Using mice that we have developed to study the fate of bulge stem cells, we will trace the movement and contribution of bulge cells in the Bnc mutant mice following hair plucking and skin injury. We will study the interaction of BNC with the EGFr pathway using mice with deleted receptors or mice expressing inhibitors of the EGFr pathway. Changes in proliferation, differentiation and migration will be assessed in both in vitro and in vivo assays. Overall, our research will discern the effect of deleting Bnc-1 and Bnc-2 in the cutaneous epithelium. The role of Bnc’s in the EGFr pathway will be discerned. The studies will impact on understanding stem cell biology and the role of Bnc’s in wound healing, hair cycling and skin regeneration.

我们的长期目标是了解核素基因在皮肤和头发中的作用