The Atg1/ULK complex functions as the most upstream factor among Atg proteins to initiate autophagy. ATG101 is a constitutive component of the Atg1/ULK complex in most eukaryotes except for budding yeast, and plays an essential role in autophagy; however, the structure and functions of ATG101 were largely unknown. Recently, we determined the crystal structure of fission yeast Atg101 in complex ...

Autophagy is a catabolic process regulated by the orchestrated action of the autophagy-related (ATG) proteins. Recent work indicates that some of the ATG proteins also have autophagy-independent roles. Using an unbiased siRNA screen approach, we explored the extent of these unconventional functions of ATG proteins. We determined the effects of the depletion of each ATG proteome component on the...

Immunosuppression with antithymocyte globulin (ATG) or cyclosporine (CSA) can be used to treat the cytopenia associated with myelodysplastic syndrome (MDS). Previously, we identified HLA-DR15, younger age, and shorter duration of red cell transfusion dependence as pretreatment variables that correlate significantly with a response. Using these pretreatment variables we have devised a simple met...

An antigen-specific suppressive T-cell factor was extracted from physically disrupted thymocytes and spleen cells of mice that had been immunized with soluble protein antigens. The factor, when inoculated into syngeneic normal mice, could induce a significant suppression of IgG antibody response against a hapten coupled to the carrier protein by which the donor of the suppressor factor was immu...

Autophagy is directed by numerous distinct autophagy-related (Atg) proteins. These transmit starvation-induced signals to lipids and regulatory proteins and assemble a double-membrane autophagosome sequestering bulk cytoplasm and/or selected cargos destined for degradation upon autophagosome fusion with a vacuole or lysosome. This Review discusses the structural mechanisms by which Atg proteins...

B16 mouse melanoma cells (clone BS59) grown in 1 to 3 ¿ig of 5-bromodeoxyuridine (BUdR) per ml form few or no tumors in C57BL/6J adult mice when injected subcutaneously in doses at which untreated cells always form tumors. Injections of BUdR-grown cells protect adult mice against melanoma. Melanoma cells grown in 1/ig of BUdR per ml for almost 1 year (clone C3471) retain a plating efficiency s...

A type-C RNA virus has been isolated that replicates readily in human and other primate cells. It was obtained from a human rhabdomyosarcoma cell (RD) that had been serially transplanted in immunosuppressed NIH Swiss mice, a strain of mouse from which infectious type-C virus has not been isolated. Various other human tumor cells, similarly transplanted, remained free of overt type-C virus expre...

AUTOPHAGY-RELATED PROTEIN (ATG) 8-FAMILY INTERACTING MOTIF IN ATG3 MEDIATES THE ATG3-ATG8 INTERACTION AND IS CRUCIAL FOR THE CYTOPLASM-TO-VACUOLE TARGETING PATHWAY* Masaya Yamaguchi, Nobuo N. Noda, Hitoshi Nakatogawa§, Hiroyuki Kumeta, Yoshinori Ohsumi, and Fuyuhiko Inagaki Department of Structural Biology, Graduate school of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Integ...

BACKGROUND Regulatory T cells have been suggested to down-regulate the alloimmune response. The aim of this prospective open study was to evaluate the effects of different inductive agents on peripheral blood regulatory T cells in kidney transplant patients and to analyse their association with short-term graft outcome. METHODS Regulatory and effector T cell numbers in peripheral blood were d...

Background Rabbit antithymocyte globulin (rATG) is the most widely used kidney transplant induction immunotherapy in the United States. It was recently Food and Drug Administration approved for this indication with typical dose recommendations of 1.5 mg/kg for up to 7 days given via a central line. Methods We theorized that reduced rATG dosing when compared with conventional dosing (6-10.5 mg...