SUMMARY PARAGRAPH for LST8
LST8 encodes an essential protein that is involved in the processes of TOR-mediated signaling and cellular response to a loss of mitochondrial function (also known as the retrograde response; 3, 4, 2). Lst8p is a subunit of both TOR complex 1 (TORC1) and TOR complex 2 (TORC2), which are involved in the regulation of cell growth in response to nutrient availability and cellular stresses (5, 4, 6). In addition to Lst8p, TORC1 consists of Kog1p, Tco89p, and either Tor1p or Tor2p, while TORC2 contains Avo1p, Avo2p, Tsc11p, Bit61p, Slm1p, Slm2p, and Tor2p (4, 7, 8). Because Lst8p appears to negatively regulate retrograde response at two distinct points in the pathway, and not all cellular Lst8p is associated with the TOR complexes, it is postulated that the role of Lst8p in mediating retrograde signaling is independent of its role as a component of the TORC1 and TORC2 complexes (3, 9, 4).
TORC1 modulates translation initiation, inhibits protein turnover, contributes to meiosis, mediates the induction of autophagy, and represses the transcription of specific genes that are induced by nutrient starvation (5, 4, 6, 10, 11, 12, 5, 13, 14, 15). Under nutrient-rich conditions, TORC1 inhibits the function of transcriptional activators that are involved in nitrogen catabolite-repression (e.g., Gat1p, Gln3p; 16, 17), stress-response (e.g., Msn2p, Msn4p; 18), ribosome biosynthesis (e.g., Crf1p, Fhl1p, Spf1p; 19, 20), and retrograde response (e.g., Rtg1p, Rtg3p; 21, 22), usually by affecting the cellular translocation of these transcription factors.
TORC2 is involved in regulating actin cytoskeleton polarization during cell cycle progression, cell wall integrity, and receptor endocytosis (23, 24). Lst8p associates with TORC2 by binding to the C-terminus of Tor2p; this interaction is necessary for activating the kinase function of Tor2p and therefore of TORC2 (25).
Loss of Lst8p function results in rapamycin hypersensitivity, cell wall instability, depolarization of the actin skeleton, and an inability to take up amino acids (2, 4, 1). Additionally, lst8 mutations are synthetically lethal in combination with mutations in the secretory pathway gene SEC13 (1). LST8 is conserved in higher eukaryotes with 28% amino acid identity between the yeast and human homologs (1). TORC1 and TORC2 and their related functions are also conserved in higher eukaryotic organsisms (4). In Drosophila, C. elegans, and mammals, TOR activity has been shown to participate in the additional processes of apoptosis, hypoxia, and aging (reviewed in 26, 27).
Last updated: 2005-11-03