Aberrant sialylation is closely associated with the malignant phenotype of cancer cells including metastatic potential and invasiveness. However, its biological significance and molecular mechanisms have yet to be fully elucidated. To determine causes and consequences, we have focused attention on mammalian sialidases, which cleave sialic acids from gangliosides and glycoproteins. The four types of human sialidases identified to date behave in different manners during carcinogenesis. One, found in the lysosomes, shows down-regulation in cancers, promoting anchorage-independent growth and contributing to metastatic ability, while another, found in the plasma membranes, exhibits marked up-regulation, resulting in suppression of apoptosis. The present review summarizes mostly our results on aberrant expression of sialidases and their possible roles in cancer progression.
Bone is a dynamic tissue, in which bone formation by osteoblasts and bone resorption by osteoclasts continue throughout life. In 1998, we molecularly cloned osteoclast differentiation factor (ODF), a long-thought factor responsible for osteoclast formation. This review article describes how Japanese scientists contributed to osteoclast biology before and after the discovery of ODF. This review article is based on the Louis V. Avioli Memorial Lecture of the American Society for Bone and Mineral Research (ASBMR) held in Honolulu in September, 2007.
Nucleotide sequencing of the entire genomes was completed in the 1980s for most members of the Paramyxoviridae. It then became a new common task with challenge for researchers in the field to establish a system to recover the virus entirely from cDNA, thereby allowing reverse genetics (free manipulation of the viral genome). Using Sendai virus, we established a system of incomparable virus recovery efficiency early on. This technology was then fully exploited in answering a series of long-held questions. In particular, two accessory genes whose functions had remained enigmatic were demonstrated to encode special functions critical in viral in vivo pathogenesis producing fatal pneumonia in mice, although dispensable in virus replication at the in vitro cellular level. Their in vivo functions were found to counteract the two respective facets of the antiviral state induced by interferons and an interferon regulatory factor 3-dependent but yet unknown effector. These achievements appear to have facilitated a scientific trend where the accessory genes are a focus of active investigation in studies on other paramyxoviruses and opened up a new common ground shared between virology and immunology.
The X-ray crystal structure of natural commelinin is investigated. The results demonstrate that commelinin is a tetranuclear (4 Mg2+) metal complex, in which two Mg2+ ions chelate to six anthocyanin molecules, while the other two Mg2+ ions bind to six flavone molecules, stabilizing the commelinin complex, a new type of supramolecular complex.