Role of SOX2 O-GIcNAcylation in pluripotency

SOX2 O-GlcNAcNA 酰化在多能性中的作用

• 批准号: 9288190
• 负责人: BARBARA PANNING
• 金额: $ 31.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-06 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9288190
• 关键词: Acetyl Coenzyme A; Adult; Affect; Alpha Cell; Anabolism; Binding; Biological; Cell Cycle; Cell Differentiation process; Cell Nucleus; Cell Proliferation; Cell Therapy; Cells; Chemicals; Chromatin; Couples; Cues; Cytosol; Data; Development; Distributional Activity; ES Cell Line; Embryonic Development; Ensure; Enzymes; Epiblast; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genetic Transcription; Glucosamine; Glucose; Glutamine; Growth; Hexosamines; Homeostasis; Impairment; Light; Link; Mammals; Maps; Mass Spectrum Analysis; Mediating; Metabolic; Metabolic Pathway; Metabolism; Methods; Mitochondria; Modeling; Modification; Molecular; Molecular Models; Monitor; Mus; Mutation; Mutation Analysis; Nutrient; Nutritional; O-GlcNAc transferase; Output; Pathway interactions; Pluripotent Stem Cells; Poly(ADP-ribose) Polymerases; Polymerase; Post-Translational Protein Processing; Proteins; Regulation; Ribose; Role; Serine; Signal Pathway; Signal Transduction; Signaling Molecule; Site; Source; Stem cells; Stress; Testing; Threonine; ataxia telangiectasia mutated protein; cell type; detection of nutrient; embryonic stem cell; experimental study; genome-wide; insight; molecular modeling; mutant; pluripotency; protein protein interaction; public health relevance; response; self-renewal; sugar; therapy development; transcription factor

 DESCRIPTION (provided by applicant): Transcription factors are central for establishing the cell type-specific gene expression patterns that characterize each of the hundreds of different cell types in developing and adult mammals. Transcription factors are often regulated by signaling pathways, which affect the activity of these factors and ensure appropriate transcriptional responses to developmental and environmental cues. Our preliminary studies indicate that a transcription factor central to embryonic stem cell self-renewal, SOX2, is modified by addition of an O-linked N-acetylglucosamine sugar to serine residue 248 and threonine residue 213. This modification is mediated by the enzyme OGT, which is a central player in the nutrient sensing pathway that detects levels of glucose and other nutrients. We propose to investigate the role of this post-translational modification of SOX2 in self-renewal, to better understand how metabolic pathways impact gene expression in pluripotent cells.