Mechanism of action of the v-erb A oncogene of AEV.

AEV 的 v-erb A 癌基因的作用机制。

基本信息

批准号：
7186526
负责人：
Martin L. Privalsky
金额：
$ 30.06万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-02-07 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7186526
关键词：
Accounting Acetylation Acute Acute Erythroblastic Leukemia Acute Promyelocytic Leukemia Adoption Affect Affinity Agonist Alkaline Phosphatase Alternative Splicing Amino Acid Receptors Amino Acid Sequence Amino Acid Substitution Amino Acids Anchorage-Independent Growth Antisense RNA Apoptosis Apoptotic Architecture Area Arsenic Arsenic Trioxide Avidity Belief Binding Binding Sites Biological Biological Process Birds Bone Marrow C-terminal Ca(2+)-Calmodulin Dependent Protein Kinase Calcium Cataloging Catalogs Cell Nucleus Cells Chimera organism Chimeric Proteins Chromatin Chromosomal translocation Clinical Treatment Cloning Complement component C1s Condition Consensus Conventional (Clear Cell) Renal Cell Carcinoma Cultured Cells Cytoplasm DNA DNA Binding DNA Sequence Defect Derivation procedure Development Direct Repeats Disease Distant Dominant-Negative Mutation Endocrine Endocrine System Diseases Epidermal Growth Factor Receptor Erythroid Erythroid Cells Event Evolution Exhibits Family Feedback Fibroblasts Frequencies Funding Future Gagging Gene Expression Gene Targeting Generations Genes Genetic Genetic Transcription Genome Genomics Goals Grant Growth Growth Factor Growth Factor Receptors Hand Helix (Snails)Heterodimerization Homeostasis Homo Hormonal Hormone Receptor Hormones Human Hypothalamic structure In Vitro Incidence Inherited Intervention Investigation Laboratories Lead Lesion Leukemic Cell Leukocytes Ligands Link Liver MAP Kinase Modules Malignant Neoplasms Malignant neoplasm of liver Maps Mediating Messenger RNA Methodology Methods Mitogen-Activated Protein Kinases Mitogens Modeling Molecular Molecular Cloning Molecular Conformation Mutate Mutation Neoplasms Neurons Normal Cell Nuclear Nuclear Hormone Receptors Nuclear Receptors Numbers Oncogene Proteins Oncogenes Oncogenic Organism Orphan Pan Genus Pathogenicity Pathway interactions Pattern Peripheral Phenotype Phosphorylation Phosphorylation Site Phosphotransferases Physiology Pituitary Gland Play Positioning Attribute Primary carcinoma of the liver cells Principal Investigator Procedures Process Promega Property Protein Dephosphorylation Protein Isoforms Protein Kinase Proteins Protocols documentation Public Health Publications Publishing RNA Splicing RXR Range Recruitment Activity Refractory Regulation Regulatory Pathway Relative (related person)Reporter Reporting Repression Research Research Personnel Resistance Response Elements Retinoic Acid Receptor Retinoid Receptor Retroviridae Role Scotland Series Shrimp Signal Pathway Signal Transduction Signal Transduction Pathway Site Somatic Mutation Specific qualifier value Specificity Suggestion Surface Symptoms Synapses Syndrome Technology Testing Therapeutic Intervention Thinking Thyroid Hormone Receptor Thyroid Hormone Receptor Beta Thyroid Hormone Resistance Syndrome Thyroid Hormones Time Tissues Transcript Transcriptional Activation Transcriptional Regulation Transgenic Mice Translations Triiodothyronine Receptors Tumor Cell Line Tumor Suppressor Proteins Universities Variant Vertebrates Viral Vitamin D3 Receptor Work base calmodulin-dependent protein kinase IV cancer cell cancer risk cell type chromatin immunoprecipitation combinatorial concept dimer ear helix gene repression human NCOR1 protein human disease human tissue improved in vivo inhibitor/antagonist interest leukemia leukemogenesis mutant neoplastic neurochemistry non-oncogenic notch protein novel paralogous gene prevent progenitor programs promoter receptor receptor binding receptor function research study response retinoic acid receptor alpha transcription factor transcription factor PML tumor tumor initiation tumor progression tumorigenesis ward

Accounting Acetylation Acute Acute Erythroblastic Leukemia Acute Promyelocytic Leukemia Adoption Affect Affinity Agonist Alkaline Phosphatase Alternative Splicing Amino Acid Receptors Amino Acid Sequence Amino Acid Substitution Amino Acids Anchorage-Independent Growth Antisense RNA Apoptosis Apoptotic Architecture Area Arsenic Arsenic Trioxide Avidity Belief Binding Binding Sites Biological Biological Process Birds Bone Marrow C-terminal Ca(2+)-Calmodulin Dependent Protein Kinase Calcium Cataloging Catalogs Cell Nucleus Cells Chimera organism Chimeric Proteins Chromatin Chromosomal translocation Clinical Treatment Cloning Complement component C1s Condition Consensus Conventional (Clear Cell) Renal Cell Carcinoma Cultured Cells Cytoplasm DNA DNA Binding DNA Sequence Defect Derivation procedure Development Direct Repeats Disease Distant Dominant-Negative Mutation Endocrine Endocrine System Diseases Epidermal Growth Factor Receptor Erythroid Erythroid Cells Event Evolution Exhibits Family Feedback Fibroblasts Frequencies Funding Future Gagging Gene Expression Gene Targeting Generations Genes Genetic Genetic Transcription Genome Genomics Goals Grant Growth Growth Factor Growth Factor Receptors Hand Helix (Snails)Heterodimerization Homeostasis Homo Hormonal Hormone Receptor Hormones Human Hypothalamic structure In Vitro Incidence Inherited Intervention Investigation Laboratories Lead Lesion Leukemic Cell Leukocytes Ligands Link Liver MAP Kinase Modules Malignant Neoplasms Malignant neoplasm of liver Maps Mediating Messenger RNA Methodology Methods Mitogen-Activated Protein Kinases Mitogens Modeling Molecular Molecular Cloning Molecular Conformation Mutate Mutation Neoplasms Neurons Normal Cell Nuclear Nuclear Hormone Receptors Nuclear Receptors Numbers Oncogene Proteins Oncogenes Oncogenic Organism Orphan Pan Genus Pathogenicity Pathway interactions Pattern Peripheral Phenotype Phosphorylation Phosphorylation Site Phosphotransferases Physiology Pituitary Gland Play Positioning Attribute Primary carcinoma of the liver cells Principal Investigator Procedures Process Promega Property Protein Dephosphorylation Protein Isoforms Protein Kinase Proteins Protocols documentation Public Health Publications Publishing RNA Splicing RXR Range Recruitment Activity Refractory Regulation Regulatory Pathway Relative (related person)Reporter Reporting Repression Research Research Personnel Resistance Response Elements Retinoic Acid Receptor Retinoid Receptor Retroviridae Role Scotland Series Shrimp Signal Pathway Signal Transduction Signal Transduction Pathway Site Somatic Mutation Specific qualifier value Specificity Suggestion Surface Symptoms Synapses Syndrome Technology Testing Therapeutic Intervention Thinking Thyroid Hormone Receptor Thyroid Hormone Receptor Beta Thyroid Hormone Resistance Syndrome Thyroid Hormones Time Tissues Transcript Transcriptional Activation Transcriptional Regulation Transgenic Mice Translations Triiodothyronine Receptors Tumor Cell Line Tumor Suppressor Proteins Universities Variant Vertebrates Viral Vitamin D3 Receptor Work base calmodulin-dependent protein kinase IV cancer cell cancer risk cell type chromatin immunoprecipitation combinatorial concept dimer ear helix gene repression human NCOR1 protein human disease human tissue improved in vivo inhibitor/antagonist interest leukemia leukemogenesis mutant neoplastic neurochemistry non-oncogenic notch protein novel paralogous gene prevent progenitor programs promoter receptor receptor binding receptor function research study response retinoic acid receptor alpha transcription factor transcription factor PML tumor tumor initiation tumor progression tumorigenesis ward

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项目摘要

We propose to better understand the mechanisms of action of the v-erb A oncogene, and to relate the role of v-erb A in viral neoplasia to events in normal differentiation and in human disease. V-erb A, an oncogene in the avian erythroblastosis retrovirus genome, participates in erythroid leukemogenesis and alters the growth properties of infected fibroblasts. V-erb A is a mutant, transduced copy of a normal cell gene (c-erb A) encoding a thyroid hormone receptor. Thyroid hormone receptors are ligand-regulated transcription factors, and belong to a larger family of nuclear receptors that play key roles in vertebrate development, homeostasis, and differentiation. Naturally occurring mutations in nuclear receptors have been implicated in important human endocrine and neoplastic diseases, including hepatocellular carcinoma, acute promyelocytic leukemia, renal clear cell carcinoma, and resistance to thyroid hormone syndrome. In many cases these mutant receptors, like v-Erb A, can act as dominant negatives. An important component of our research extends to understanding the molecular defects in these human diseases, and why different receptor mutations result in different diseases. We propose four specific aims to investigate these questions: SPECIFIC AIM A. We will identify v-Erb A and PML-RARalpha target genes. SPECIFIC AIM B. We will elucidate how v-Erb A represses target gene expression once bound to a target DMA SPECIFIC AIM C. We will elucidate how v-Erb A function is altered by other signal transduction pathways operative in the erythroleukemic cell SPECIFIC AIM D. We will use v-Erb A as a model to improve our understanding of the actions of the aberrant nuclear receptors involved in human disease. Relevance to public health: This research will help establish how alterations in normal genes can lead to cancers and other diseases. It will also contribute to our understanding of how hormone receptors function in normal physiology and development.

我们建议更好地了解V-ERB A癌基因的作用机制，并联系起来的作用病毒性肿瘤中的V-ERB A与正常分化和人类疾病中的事件。 v-erb a，癌基因鸟类红细胞肌动病毒基因组，参与红细胞性白血病发生并改变生长感染成纤维细胞的特性。 V-ERB A是正常细胞基因的突变体，转导的副本（C-ERB A）编码甲状腺激素受体。甲状腺激素受体是配体调节的转录因子，并属于较大的核受体家族，在脊椎动物发育中起关键作用，稳态和差异化。核受体中自然发生的突变已与重要的人内分泌和肿瘤疾病，包括肝细胞癌，急性临床细胞白血病，肾透明细胞癌和对甲状腺激素综合征的抗性。许多人这些突变受体（如V-ERB A）可以充当主要的负面因素。我们的重要组成部分研究扩展到了解这些人类疾病中的分子缺陷，以及为什么不同受体突变导致不同的疾病。我们提出了四个特定的目的来研究这些问题：特定目标A.我们将识别V-ERB A和PML Raralpha靶基因。具体目标B.我们将阐明V-ERB A抑制目标基因表达曾经结合到目标 DMA 具体目的C.我们将阐明v-erb A函数如何通过其他信号转导途径改变红血球细胞中的手术具体目的D.我们将使用V-ERB A作为模型来提高我们对行为的理解涉及人类疾病的异常核受体。与公共卫生有关：这项研究将有助于确定正常基因的变化如何导致癌症和其他疾病。它也将有助于我们对激素受体如何发挥作用的理解在正常的生理和发展中。