Cell Signaling & Neuroscience Transcription Activation

Slides Programmed Cell Death Activation and Inhibition of Apoptosis Mitochondria in Apoptosis ATM/p53 Signaling Pathway Caspase Cascade Caspase Activation Intrinsic Pathway Granzyme B FAS and Related Proteins Fas Signaling G1, and S Phases G2 and M Phases Regulatory Cascade The p53 Signaling Pathway Cytokines and Growth Factors Structures of Activin and Inhibin Structures of Chemokine Receptors Angiopoietins EGFR Signaling Pathway Transmembrane Precursors of EGF Possible Receptor Combos and Ligand Actions of Flt-3/Flk-2 Hedgehog and BMI1 IGF Regulation of Apoptosis IL-13 and IL-4 receptor IL-18 Production Neurotrophins and Their Receptors TrkA GDNF Family with Receptors PDGF Receptors and Actions TGF-beta Signaling BMP Signaling TNF Signaling TNF-α and TNF-β Proposed Balance Between TNF Superfamily Structure of Receptors VEGF Receptor and Ligands Prolactin Regulation Insulin Pathway Glucocorticoid Receptor Signaling Vascular Endothelial Cell Interactions Integrin Signaling in Cell Survival VEGF Receptor Signaling MMPs and Cytokines Events Leading to Angiogenesis Transcription Factors Nuclear Complex Targeting Jak/Stat Pathway STAT3 PPAR Formation of Nucleosomes DNA Compaction Early Response Events Cell Cycle Checkpoint Linkage between DNA Repair and Chromatin Modification Functions of WRN, BLM and MRE11 mRNP Transport Importinα - Importinβ Pathway Modular Structure of Transcription factors Transcription Activation by Nuclear Receptors Coupled RNA Splicing and Nuclear Export RNA Polyadenylation Mammalian mRNA Polyadenylation RNA Maturation Epigenetic Control Phosphorylation-driven Initiation-Elongation cAMP Metabolism cGMP Metabolism G-Protein Signaling T Cell Receptor B Cell Receptor Monovalent Ion Channels Activation/Inactivation Ligand-Gated Ion Channel Aquaporin Channel Structure Calcium Channel Structure Calcium Channel Pore Region Chloride Channel HCN Channel 2TM Potassium Channel Structure 6TM Potassium Channel Structure Sodium Channel Structure Sodium Channel Pore Region PTEN Pathway Lipids in Cell Signaling Inositol Phosphates Phosphatidic Acid Inositol Phospholipids ABC Transporters ABC-ATPases BSEP MRP1 β-Amyloid Plaques Notch Secretase Second Messenger Systems Limbic Reward Circuit Major Pathways in the CNS Endothelin Signaling NPY and Catecholamines Ascending Pain Pathway Modulation of Pain Transmission Mechanism of Action Fig. A Mechanism of Action Fig. B Drug Activation of Dopaminergic GABAB Receptor Oxidative Stress nNOS eNOS iNOS Nitric Oxide Proteasome/Ubiquitination Formation of Activated 20S Proteasome Ubiquitin Pathway MAP Kinase Cascades AKT Signaling Pathways Activated by VEGF

Transcription Activation by Nuclear Receptors

Retinoid X receptor (RXR) and Retinoic Acid receptor (RAR) are nuclear receptors that bind either all trans-retinoic (tRA) or 9-cis-retinoic acid (9-cis-RA). In the absence of ligand, corepressors, such as Nuclear Receptor Corepressor (NCoR), Silencing Mediator of Retinoid and Thyroid Hormone Receptor (SMRT), and Histone Deacetylase-1 (HDAC-1) associate with the RAR:RXR heterodimer complex and repress transcription. The histone deacetylase activity of the complex helps maintain tight association between the deacetylated histones and chromatin that results in this repression.

When tRA or 9-cis-RA binds to the RAR:RXR complex, a conformational change in the receptors causes the dissociation of the corepressors and subsequent recruitment and binding of coactivators such as Steroid Receptor Coactivator-1 (SRC-1), Glucocorticoid Receptor Interacting Protein-1 (GRIP-1), CREB Binding Protein (CBP) and CBP-Associated Factor (PCAF). This receptor:coactivator complex activates histone acetyltransferase (HAT). Acetylated histones dissociate from the chromatin and allow for the basal transcription machinery complex to bind to DNA and activate transcription of target genes.

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