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Role of the candidate protein methyltransferase METTL18 in cancer biology

候选蛋白甲基转移酶 METTL18 在癌症生物学中的作用

基本信息

批准号：
10388029
负责人：
Joel Francis
金额：
$ 3.92万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-10 至 2025-02-09
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10388029
关键词：
Agar Anchorage-Independent Growth Antibodies Arginine Biochemical Biological Biological Assay Biological Process Biology Cancer Biology Cancer Patient Cancer cell line Cell Line Cell physiology Cells Collaborations Consequentialism Data Data Set Databases Defect Enzymes Event Gene Expression Genetic Translation Graduate Education Histidine Human Human Genome In Vitro Investigation Knock-out Knowledge Laboratories Letters Luciferases Lysine Malignant Neoplasms Mammals Measures Mentors Methylation Methyltransferase Modification Molecular Mus Neoplasm Metastasis Normal tissue morphology Pathway interactions Patients Phenotype Physiological Polyribosomes Positioning Attribute Post-Translational Protein Processing Primary Neoplasm Protein Biosynthesis Protein Methylation Protein Methyltransferases Proteins Proteome Proteomics Publications Regulation Research Project Grants Ribosomal Proteins Role Sampling Signal Transduction Source Stomach TP53 gene Testing Tissues Translation Initiation Universities Variant Work antibody libraries cancer cell clinically actionable experience experimental study gastric cancer cell human disease in vivo interdisciplinary approach mRNA Expression malignant stomach neoplasm mouse model mutant novel programs protein function reconstitution ribosome profiling tumorigenesis yeast protein

项目摘要

Project Summary Covalent post-translational protein modifications contribute to all aspects of cell physiology and are a primary source of protein functional diversity in mammals. The aberrant regulation of these modifications, as well as the enzymes that generate them, is a common feature of human disease, including cancer. There are more than 150 protein methyltransferases encoded in the human genome, and a growing number of human proteins, including several with established roles in signaling and cancer, are known to harbor functional post-translational methylation events. Most methylation events occur on either lysine or arginine residues; however, our lab and others have recently discovered that histidine methylation occurs on over 200 human proteins as well. Still, very little is known about the molecular, signaling and biological consequences associated with protein histidine methylation. This proposal focuses on a protein histidine methyltransferase (PHMT), METTL18, and its role in cancer. In preliminary work I found that METTL18 methylates the ribosomal protein rpL3 at position His245 in numerous cell lines and mouse tissue. I also have evidence that METTL18 regulates protein synthesis and oncogenesis. Here I propose to use multi-disciplinary approaches, including biochemical, proteomic and cell biological strategies to (1) investigate the molecular and biological function of METTL18 catalytic activity and (2) characterize the physiologic role of METTL18 in gastric cancer. The proposed project will be executed in the laboratory of Dr. Or Gozani at Stanford University. Dr. Gozani is an experienced mentor and a leader at the intersection of the fields of protein methylation and cancer biology. He and the Stanford University Department of Biology are well-suited to support my research project and graduate education.

项目总结