TOR complex 1 includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in Saccharomyces cerevisiae.
The Tor1p and Tor2p kinases, targets of the therapeutically important antibiotic rapamycin, function as components of two distinct protein complexes in yeast, termed TOR complex 1 (TORC1) and TORC2. TORC1 is responsible for a wide range of rapamycin-sensitive cellular activities and contains, in addition to Tor1p or Tor2p, two highly conserved proteins, Lst8p and Kog1p. By identifying proteins that co-purify with Tor1p, Tor2p, Lst8p, and Kog1p, we have characterized a comprehensive set of protein-protein interactions that define further the composition of TORC1 as well as TORC2. In particular, we have identified Tco89p (YPL180w) and Bit61p (YJL058c) as novel components of TORC1 and TORC2, respectively. Deletion of TOR1 or TCO89 results in two specific and distinct phenotypes, (i) rapamycin-hypersensitivity and (ii) decreased cellular integrity, both of which correlate with the presence of SSD1-d, an allele of SSD1 previously associated with defects in cellular integrity. Furthermore, we link Ssd1p to Tap42p, a component of the TOR pathway that is believed to act uniquely downstream of TORC1. Together, these results define a novel connection between TORC1 and Ssd1p-mediated maintenance of cellular integrity.
Reinke
Aaron
A
Section of Molecular and Cellular Biology and Center for Genetics and Development, Division of Biological Sciences, University of California, Davis, California 95616, USA.
Anderson
Scott
S
McCaffery
J Michael
JM
Yates
John
J
Aronova
Sofia
S
Chu
Stephanie
S
Fairclough
Stephen
S
Iverson
Cory
C
Wedaman
Karen P
KP
Powers
Ted
T
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000737:chemistry; D017353:Gene Deletion; D013058:Mass Spectrometry; D016253:Microscopy, Immunoelectron; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D013696:Temperature
D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D005656:Fungal Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; C485219:Ssd1 protein, S cerevisiae; C100984:TAP42 protein, S cerevisiae; C485218:Tco89 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae