Abstract
Target of rapamycin complexes (TORCs), which are vital for nutrient utilization, contain a catalytic subunit with the phosphatidyl inositol kinase-related kinase (PIKK) motif. TORC1 is required for cell growth, while the functions of TORC2 are less well understood. We show here that the fission yeast Schizosaccharomyces pombe TORC2 has a cell cycle role through determining the proper timing of Cdc2 Tyr15 dephosphorylation and the cell size under limited glucose, whereas TORC1 restrains mitosis and opposes securin–separase, which are essential for chromosome segregation. These results were obtained using the previously isolated TORC1 mutant tor2-L2048S in the phosphatidyl inositol kinase (PIK) domain and a new TORC2 mutant tor1-L2045D, which harbours a mutation in the same site. While mutated TORC1 and TORC2 displayed diminished kinase activity and FKBP12/Fkh1-dependent rapamycin sensitivity, their phenotypes were nearly opposite in mitosis. Premature mitosis and the G2–M delay occurred in TORC1 and TORC2 mutants, respectively. Surprisingly, separase/cut1—securin/cut2 mutants were rescued by TORC1/tor2-L2048S mutation or rapamycin addition or even Fkh1 deletion, whereas these mutants showed synthetic defect with TORC2/tor1-L2045D. TORC1 and TORC2 coordinate growth, mitosis and cell size control, such as Wee1 and Cdc25 do for the entry into mitosis.
Highlights
Understanding the relationship between cell division and growth is important in biology
The mammalian TOR catalytic subunit is the sole target of rapamycin through FKBP12 in mammals
To determine whether Tor1 is associated with only TORC2, immunoprecipitations were done
Summary
Understanding the relationship between cell division (increase in cell number) and growth (increase in cell volume or mass) is important in biology. It is well established that cyclin-dependent protein kinase (CDK) is the main regulator of division, while the target of rapamycin (TOR) complex regulates cell growth [1,2]. Commonly used in organ transplantation [3] It was originally isolated as an antifungal compound produced by a bacterium [4]. It displays antiproliferative properties, prolongs the life of model animals, and might be useful in the treatment of certain cancers. Rapamycin binds to FK-binding protein (FKBP12, a peptidyl-prolyl cis-trans isomerase), which inhibits the TOR kinase complex (TORC) through direct binding [5]. The mammalian TOR (mTOR) catalytic subunit is the sole target of rapamycin through FKBP12 in mammals. Frp (an FKBP12 homologue), Tor and Tor participate in rapamycin toxicity [6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
