Partenaires
Rechercher
Accueil du site > Animations Scientifiques > Séminaires 2007 > Small Molecule Modulators of Chromatin Modifying Enzymes : To Probe Eukaryotic Transcription and To Target Diseases
Small Molecule Modulators of Chromatin Modifying Enzymes : To Probe Eukaryotic Transcription and To Target Diseases
Orateur :
Tapas K. Kundu, Transcription an Disease Laboratory and, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, India
Salle :
118
Sujet :
Human genes are organized into a highly compact dynamic nucleoprotein complex called chromatin, which consists of histones and associated non-histone proteins. Though apparently repressive, the precise organization of chromatin is essential for the entire DNA-templated phenomenon inside the cell. Alteration in chromatin organization modulates the expression of underlying genes. The post-transitional modification (eg. reversible acetylation, methylation and phosphorylation) of chromatin proteins plays crucial roles in the dynamic organization chromatin template for all he cellular phenomenon including transcription. Dysfunction of these enzymes is often associated with several diseases like Cancer, Asthma, Diabetes and several Neurodegenerative disorders. Small molecule modulators of HATs, HDACs, and HMTases thus are new potential therapeutic molecules. We have discovered several small molecule modulators of acetyltransferases, which include anacardic acid, garcinol, curcumin, as HAT inhibitors and CTPB as activator. CTPB is the only known small molecule HAT activator histone acetyltransferases, which is specific for the p300 HAT activity.
Most recently based on the natural cell permeable HAT inhibitor we have synthesized couple of p300 specific cell permeable inhibitors which significantly non-toxic as compared to parent compound. We have recently found a potent and specific inhibitor of histone arginine methyltransferase, CARM1. The role of this compound on methylation dependent activation of p53 responsive genes and its functional consequence is being investigated. The significance of these small molecular modulators is immense with respect to the as yet unexplored field of EPIGENETICS based drugs. These compounds would be useful as biological switching molecules for probing into the role of HATS/HDACs/HMTases in gene regulation, and may also serve as new chemical entities for the development of new drugs.
Dans la même rubrique :
- Discrete breathers in nonlinear network models of proteins
- Conservative behavior of the biological complex system [Telomeres-Telomerase-Prolifération]
- Linking molecular mechanisms to the organism’s physiology using transcriptomics
- Electron-donor modified nanoparticles for selected cell labeling and photodynamic therapy
- Soutenance d’HDR:Les modes normaux de basse fréquence des protéines
- Human monoclonal antibodies against viruses and cancer
- Vésicules biomimétiques à base de PIP2 pour étudier des interactions protéines membranes : application à une protéine de la famille des ERM (ezrine, radixine, moésine).
- Structural insights into base damage recognition and removal by the Fpg DNA glycosylase
- Transcription by yeast RNA polymerase III and Chromatin Remodeling
- Distinct roles of core histones, histone variants and linker histones in chromatin function
- DNA : More than just a ladder
- Chromatin dynamics in interphase
- On the role of the retroviral Gag protein and the RNA in virus assembly
- What determines the size of virus ?
- Cytoskeleton dynamics involved in cell morphology control and multicellular stability
- Molecular mechanisms of gene transcription and DNA repair in living cells
- Models for the interaction between antibiotic peptides and lipid bilayers - Modèles pour l’interaction entre des peptides antibiotiques et des bicouches lipidiques
- Exploration électrochimique de la dynamique de brins courts d’ADN ancrés sur une surface
- The nucleosome : A transparent, slippery, sticky and yet stable DNA-protein complex
- Histone H1 is a architectural molecule required for chromatin compaction, and is redundant for gene repression
