Autophagy involvement in oncogenesis.

Various clinical and experimental findings have revealed the causal relationship between autophagy failure and oncogenesis, and several mechanisms have been suggested to explain this relationship. We recently proposed two additional mechanisms: centrosome number dysregulation and the failure of autophagic cell death. Here, we detail the mechanical relationship between autophagy failure and oncogenesis.

Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages.

Disturbed activation of autophagy is implicated in the pathogenesis of inflammatory bowel disease. Accordingly, several autophagy-related genes have been identified as Crohn's disease susceptibility genes. We screened the autophagy activators from a library including 3,922 natural extracts using a high-throughput assay system.

Association Between Atg5-independent Alternative Autophagy and Neurodegenerative Diseases.

Autophagy is a cellular process that degrades intracellular components, including misfolded proteins and damaged organelles. Many neurodegenerative diseases are considered to progress via the accumulation of misfolded proteins and damaged organelles; therefore, autophagy functions in regulating disease severity. There are at least two types of autophagy (canonical autophagy and alternative autophagy), and canonical autophagy has been applied to therapeutic strategies against various types of neurodegenerative diseases.

Prediction of intracellular targets of a small compound by analyzing peptides presented on MHC class I.

In chemical biology, the elucidation of chemical target is crucial for successful drug development. Because MHC class I molecules present peptides from intracellular damaged proteins, it might be possible to identify targets of a chemical by analyzing peptide sequences on MHC class I. Therefore, we treated cells with the autophagy-inducing chemical TMD-457 and identified the peptides presented on MHC class I.

Autophagy controls centrosome number by degrading Cep63.

Centrosome number is associated with the chromosome segregation and genomic stability. The ubiquitin-proteasome system is considered to be the main regulator of centrosome number. However, here we show that autophagy also regulates the number of centrosomes.

Gene set enrichment analysis provides insight into novel signalling pathways in breast cancer stem cells.

Background: Tumour-initiating cells (TICs) or cancer stem cells can exist as a small population in malignant tissues. The signalling pathways activated in TICs that contribute to tumourigenesis are not fully understood.

Methods: Several breast cancer cell lines were sorted with CD24 and CD44, known markers for enrichment of breast cancer TICs.

An FGF4-FRS2alpha-Cdx2 axis in trophoblast stem cells induces Bmp4 to regulate proper growth of early mouse embryos.

A variety of stem cells are controlled by the actions of multiple growth factors in vitro. However, it remains largely unclear how growth factors control the proliferation and differentiation of stem cells in vivo. Here, we describe a novel paracrine mechanism for regulating a stem cell niche in early mammalian embryos, which involves communication between the inner cell mass (ICM) and the trophectoderm, from which embryonic stem (ES) cells and trophoblast stem (TS) cells can be derived, respectively.

Essential role of Shp2-binding sites on FRS2alpha for corticogenesis and for FGF2-dependent proliferation of neural progenitor cells.

Mammalian corticogenesis occurs through a complex process that includes neurogenesis, in which neural progenitor cells proliferate, differentiate, and migrate. It has been reported recently that neurogenesis occurs in the subventricular zone (SVZ), a region previously thought to be the primary site of gliogenesis. It has been recognized that in the SVZ, intermediate progenitor cells, derived from radial glial cells that are multipotent neural stem cells, produce only neurons.

The docking protein FRS2alpha is an essential component of multiple fibroblast growth factor responses during early mouse development.

The docking protein FRS2alpha is a major mediator of fibroblast growth factor (FGF) signaling. However, the physiological role of FRS2alpha in vivo remains unknown. In this report, we show that Frs2alpha-null mouse embryos have a defect in anterior-posterior (A-P) axis formation and are developmentally retarded, resulting in embryonic lethality by embryonic day 8.

The effects of diethyldithiocarbamate and carbon disulfide on acute nephrotoxicity induced by furan, bromobenzene and cephaloridine in mice.

In previous studies (Masuda and Nakayama, 1983), diethyldithiocarbamate (DTC) and carbon disulfide (CS2) have been found to be protective against acute nephrotoxicity induced by CHCl3 and 1,1-dichloroethylene in normal and CCl4-poisoned mice, and it has been suggested that the protective action of DTC and CS2 might be mediated through inhibition of bioactivation of these nephrotoxicants in the kidney. As an extension of these studies, similar experiments were undertaken with furan, bromobenzene and cephaloridine, other nephrotoxic agents that are also thought to require metabolic activation. DTC or CS2 prevented mice from suffering renal injury induced by furan and bromobenzene, as evidenced by suppression of elevations in plasma urea nitrogen concentration and kidney calcium content and of morphologic alterations.