Principal Investigator_K.Ogata
Role of post-translational modification in transcriptional regulation
Kazuhiro Ogata
Professor, Biochemistry
researchmap
Our Aim
We analyze the regulatory mechanisms of biomacromolecules involved in transcriptional regulation from the aspect of posttranslational modifications (PTMs) at the atomic level to provide a basis for drug discovery.
Background
Organisms are maintained by the coordinated functions of many kinds of differentiated cells, where “regulated” functions are of great importance and a “deregulated” state of cells leads to a variety of disorders including cancer. The regulation of cell functions is conducted by cell signaling from the cell membrane to the nucleus with a PTM cascade employed to regulate gene expression. In this sense, drug development for diseases is considered to be an approach for the restoration of normal PTM cascades.
Research Overview
We focus on PTM cascades built for cell signaling and study the regulatory system of biomacromolecules by PTM and its failure in diseases at the atomic level. In particular, molecular structural and mutational analyses for examining roles of PTM for transcription factors (TFs) and their associated molecules are considered. Assay system for monitoring intermolecular interactions and the in silico screening system will also be introduced to find novel seeds for drug candidates.
Achievements
A crystal structure of a multiple TFs assembly composed of Ets1, Runx1 and CBFβ, which are related to hematopoiesis and leukemia, formed on the T cell specific gene enhancer, has been solved. The role of Ets1 phosphorylation, induced through calcium signaling, for the multiple TFs assemblies formed on various Ets1-target enhancers has also been examined in cells (submitted). These findings will lead to new insights into transcriptional regulation by PTM and the regulation of PTM of TFs as a new approach for drug development.