✓ Read ↠´ Characteristics of activation domains that control potency and permissiveness of activation domain binding sites. by Steven P. Rowe ò usobet.co

✓ Read ↠´ Characteristics of activation domains that control potency and permissiveness of activation domain binding sites. by Steven P. Rowe ò The Regulation Of Transcription Levels Of Specific Genes Is One Of The Fundamental Processes That Underlie Human Physiology Nearly Every Human Disease Is Caused By Transcriptional Mis Regulation Or Manifests Such Mis Regulation As An Effect This Realization Has Brought About An Interest In Fully Understanding Transcriptional Regulation And Developing Molecules Capable Of Artificially Modulating Transcription Transcriptional Regulation In A Eukaryotic Cell Depends On Than Different Proteins Acting In Concert Within This Machinery, Transcriptional Activators And Coactivators Play Two Of The Most Important Roles Transcriptional Activators Bind To Specific DNA Sequences And Then Contact, Via Their Activation Domains, Surfaces On Coactivators To Recruit The Transcriptional Machinery, Including RNA Polymerase II, And Initiate Transcription Transcriptional Coactivators Transduce Information From Activators To RNA Polymerase II Allowing For Precise Control Of Transcription Until Recently, The Prevailing Model Was That The Abilities Of Different Transcriptional Activation Domains To Up Regulate Transcription To Particular Levels Was Exclusively A Function Of Their Respective Binding Affinities For Coactivators Upon Examination Of Activation Domains That Uniquely Target The Coactivator Med, We Were Able To Demonstrate That Other Characteristics Of Activation Domains Such As Coactivator Binding Site Location And Avoidance Of Proteolytic Degradation And Non Productive Interactions Play Parts In Controlling Activation Domain Potency In Particular, We Uncovered A Second Binding Site For The XLY Activation Domain That Limits Its Interactions With Proteases And Other Proteins And Allows It To Function As A Much Potent Activation Domain Than Other Short Peptides Activation Domain Binding Sites On Coactivators Consist Of Shallow Hydrophobic Grooves That Can Interact With Several Different Activation Domains This Suggests That Such Protein Surfaces Possess Permissive Binding Profiles And That A Variety Of Non Biopolymer Scaffolds Appended With Appropriate Functionality Might Act As Artificial Activation Domains Series Of Peptidomimetic Analogs Of Known Activation Domains Were Used To Examine The Permissiveness Of An Activation Domain Binding Site From The CBP KIX Domain Through Cell Free Binding Assays And Inhibition Of Activation In A Cellular Context Activation Domain Binding Site Permissiveness Was Also Demonstrated By Our Discovery That Small Molecule Isoxazolidines Could Target The Transcriptional Machinery And Up Regulate Transcription To A Significant Degree Inside Living Cells



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