Hiroaki Kiyokawa

We are interested in the basic mechanisms of cell cycle control, cellular senescence/immortalization and malignant transformation, with a focus on protein regulation by ubiquitination. We previously demonstrated that cell cycle regulators such as p27Kip1, CDK4 and CDC25A play highly tissue-specific roles in development and oncogenesis. Ubiquitination, the covalent modification of substrate proteins with the small 76-residue protein ubiquitin, exerts diverse regulation of the fate of substrates, including the cell cycle regulators, e.g, promoting proteolysis, altering subcellular localization and modulating enzymatic activities. Our current research is aimed at revealing novel functions of ubiquitination enzymes and their substrates in development and cancer, which is expected to identify new therapeutic targets against human diseases. The laboratory uses a combination of protein engineering, proteomics, bioinformatics, cell biological techniques such as time-lapse microscopy and 3-D culture, and genetically engineered mouse models. Keywords: cell cycle, ubiquitin, ubiquitination, cancer initiation, cancer progression, knockout mice, transgenic mice, breast cancer, cyclin, diabetes, pituitary, development.