Accumulating evidence indicates that deregulated activation of mTORC1 is associated with a variety of human diseases, including cancers, diabetes and neurodegenerative disorders ( Laplante and Sabatini, 2012 Saxton and Sabatini, 2017 Zoncu et al., 2011).Īs the mTOR kinase serves as a catalytic subunit in both mTORC1 and mTORC2, the distinct substrate specificities of the two complexes are likely to be determined by the regulatory subunits unique to each complex. Mammalian TORC1 (mTORC1), whose regulatory subunits include RAPTOR (also known as RPTOR) ( Hara et al., 2002 Kim et al., 2002) and mLST8 ( Kim et al., 2003), promotes protein synthesis and other anabolic processes, while suppressing cellular catabolic processes such as autophagy. TOR forms two distinct multi-subunit complexes termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2), each of which phosphorylates specific sets of cellular substrates in response to diverse stimuli, such as nutrients and growth factors ( Laplante and Sabatini, 2012 Saxton and Sabatini, 2017 Zoncu et al., 2011). The target of rapamycin (TOR) kinase, a member of the phosphoinositide 3-kinase-related kinase (PIKK) family, is highly conserved among diverse eukaryotes as a master regulator of cell growth and metabolism ( Soulard et al., 2009 Wullschleger et al., 2006). These results strongly suggest that the TOS motif represents an evolutionarily conserved mechanism of the substrate recognition by TORC1. Furthermore, we utilized the mip1-Y533A mutation to screen the known TORC1 substrates in fission yeast and successfully identified Atg13 as a novel TOS-motif-containing substrate. The binding of the TOS motif to Mip1 is dependent on Mip1 Tyr-533, whose equivalent in RAPTOR is known to interact with the TOS motif in their co-crystals. The TOS motif in Psk1 resembles those in mammals, including the conserved phenylalanine and aspartic acid residues essential for the Mip1 interaction and TORC1-dependent phosphorylation of Psk1. In the present study, we show that the fission yeast S6 kinase Psk1 contains a TOS motif that interacts with Mip1, a RAPTOR ortholog. Despite the evolutionary conservation of TORC1, no TOS motif has been described in lower eukaryotes. The regulatory subunits of mammalian TORC1 (mTORC1) include RAPTOR (also known as RPTOR), which recruits mTORC1 substrates, such as S6K1 (also known as RPS6KB1) and 4EBP1 (EIF4EBP1), by interacting with their TOR signaling (TOS) motif. Hanford Atomic Products Operation.TOR complex 1 (TORC1) is a multi-subunit protein kinase complex that controls cellular growth in response to environmental cues. Research organization: General Electric Co., Richland, WA (USA). Atomic Energy Commission depository collection. 63 RADIATION, THERMAL, AND OTHER ENVIRON.560100* - Biomedical Sciences, Applied Studies- Radiation Effects.520302 - Environment, Aquatic- Radioactive Materials Monitoring & Transport- Aquatic Ecosystems & Food Chains- (-1987).520301 - Environment, Aquatic- Radioactive Materials Monitoring & Transport- Water- (1987).11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS.053000 - Nuclear Fuels- Environmental Aspects.(For preceding period see HW-41026.) Report Numbers: HW-42403 Other Subject(s): The status of the research program is reviewed. counting of fission products in reactor effluent the development of monitoring methods and instruments counting techniques soil chemistry waste disposal and meteorological studies.
#Fission yeast skin
irradiation on the skin of sheep, swine, and rabbits fission product absorption and metabolism in rats absorption and metabolism of reactor effluent radioisotopes in rats gastro-intestinal radiation injury in rats fission product uptake in plants genetic effects of internally deposited radioelements in yeast biological monitoring of waterfowl development of a system for the quantitative measurement by. Summary: Progress is reported in the following studies: a radio-biological-ecological survey of the Columbia River the toxicity of sodium dichromate in effluent water for chinook salmon the toxic effects of continuous low-level exposure to I/sup 131/ in sheep comparative effects of.
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