NF-κB was first identified in 1986 as a B cell-specific transcription factor inducing immunoglobulin κ light chain expression. Subsequent studies revealed that NF-κB plays important roles in development, organogenesis, immunity, inflammation, and neurological functions by spatiotemporally regulating cell proliferation, differentiation, and apoptosis in several cell types. Furthermore, studies on the signal pathways that activate NF-κB led to the discovery of TRAF family proteins with E3 ubiquitin ligase activity, which function downstream of the receptor. This discovery led to the proposal of an entirely new signaling mechanism concept, wherein K63-ubiquitin chains act as a scaffold for the signaling complex to activate downstream kinases. This concept has revolutionized ubiquitin studies by revealing the importance of the nonproteolytic functions of ubiquitin not only in NF-κB signaling but also in a variety of other biological systems. TRAF6 is the most diverged among the TRAF family proteins, and our studies uncovered its notable physiological and pathological functions.
Research on lipid peroxidation in food degradation, oil and fat nutrition, and age-related diseases has gained significant international attention for the view of improvement of societal health and longevity. In order to promote basic studies on these topics, a chemiluminescence detection-high performance liquid chromatography instrument using a high-sensitivity single photon counter as a detector was developed. This instrument enabled us to selectively detect and quantify lipid hydroperoxides, a primary product of lipid peroxidation reactions, as hydroperoxide groups at the lipid class level. Furthermore, an analytical method using liquid chromatography–tandem mass spectrometry has been established to discriminate the position and stereoisomerization of hydroperoxide groups in lipid hydroperoxides. Using these two methods, the reaction mechanisms of lipid peroxidation in food and in the body have been confirmed.
In addition to simple on/off switches for molecular activity, spatiotemporal dynamics are also thought to be important for the regulation of cellular function. However, their physiological significance and in vivo importance remain largely unknown. Fluorescence imaging technology is a powerful technique that can reveal the spatiotemporal dynamics of molecular activity. In addition, because imaging detects the correlations between molecular activity and biological phenomena, the technique of molecular manipulation is also important to analyze causal relationships. Recent advances in optical manipulation techniques that artificially perturb molecules and cells via light can address this issue to elucidate the causality between manipulated target and its physiological function. The use of light enables the manipulation of molecular activity in microspaces, such as organelles and nerve spines. In this review, we describe the chromophore-assisted light inactivation method, which is an optical manipulation technique that has been attracting attention in recent years.