Cardiac Remodeling in the Hypertrophic Heart: Signal-Dependent Regulation of the Fibrotic Gene Program by CLP-1

摘要: The response of the heart to hypertrophic stress stimuli is designed normalize function under conditions increased demand. To achieve this, must mount a genomic that itself responsive signal transduction pathways used by cells transmit signals. ability adaptively link critical how responds stress. Our laboratory has been studying molecular events involved in this adaptive linkage. studies have shown CLP-1 (Cardiac Lineage Protein-1), mouse homolog human HEXIM1, acts as “go-between” linking with response. Critical linkage HEXIM1/CLP-1’s control cyclin-dependent kinase 9 (cdk9), responsible for activating RNA polymerase (pol) II complete synthesis nascent gene transcripts. Through its cdk9, HEXIM1/CLP-1 controls transcriptional output genes regulating II, and more recent data shown, activity specific transcription factors such those small mother against decapentaplegic(smad) family, transcribe genes. Together, these observations provide strong support idea plays role controlling cardiac stimuli.