LST8/YNL006W Summary Help

Standard Name LST8 1
Systematic Name YNL006W
Feature Type ORF, Verified
Description Protein required for the transport of Gap1p; required for the transport of amino acid permease Gap1p from the Golgi to the cell surface; component of the TOR signaling pathway; associates with both Tor1p and Tor2p; contains a WD-repeat (1, 2 and see Summary Paragraph)
Name Description Lethal with Sec Thirteen 1
Chromosomal Location
ChrXIV:620067 to 620978 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All LST8 GO evidence and references
  View Computational GO annotations for LST8
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 16 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
conditional
null
reduction of function
repressible
unspecified
Resources
239 total interaction(s) for 196 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 27
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 27
  • Co-fractionation: 4
  • Co-purification: 2

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 4
  • Negative Genetic: 118
  • Phenotypic Suppression: 4
  • Positive Genetic: 26
  • Synthetic Lethality: 9
  • Synthetic Rescue: 15

Resources
Expression Summary
histogram
Resources
Length (a.a.) 303
Molecular Weight (Da) 34,034
Isoelectric Point (pI) 6.5
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIV:620067 to 620978 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..912 620067..620978 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004951
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 Contact SGD

References cited on this page View Complete Literature Guide for LST8
1) Roberg KJ, et al.  (1997) Control of amino acid permease sorting in the late secretory pathway of Saccharomyces cerevisiae by SEC13, LST4, LST7 and LST8. Genetics 147(4):1569-84
2) Chen EJ and Kaiser CA  (2003) LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway. J Cell Biol 161(2):333-47
3) Liu Z, et al.  (2001) RTG-dependent mitochondria to nucleus signaling is negatively regulated by the seven WD-repeat protein Lst8p. EMBO J 20(24):7209-19
4) Loewith R, et al.  (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10(3):457-68
5) Cardenas ME, et al.  (1999) The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev 13(24):3271-9
6) Weisman R and Choder M  (2001) The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine. J Biol Chem 276(10):7027-32
7) Reinke A, et al.  (2004) TOR complex 1 includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in Saccharomyces cerevisiae. J Biol Chem 279(15):14752-62
8) Fadri M, et al.  (2005) The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol Biol Cell 16(4):1883-900
9) Butow RA and Avadhani NG  (2004) Mitochondrial signaling: the retrograde response. Mol Cell 14(1):1-15
10) Barbet NC, et al.  (1996) TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell 7(1):25-42
11) Powers T and Walter P  (1999) Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae. Mol Biol Cell 10(4):987-1000
12) Kamada Y, et al.  (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150(6):1507-13
13) Zheng XF and Schreiber SL  (1997) Target of rapamycin proteins and their kinase activities are required for meiosis. Proc Natl Acad Sci U S A 94(7):3070-5
14) Heitman J, et al.  (1991) Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253(5022):905-9
15) Schmidt A, et al.  (1998) The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. EMBO J 17(23):6924-31
16) Shamji AF, et al.  (2000) Partitioning the transcriptional program induced by rapamycin among the effectors of the Tor proteins. Curr Biol 10(24):1574-81
17) Beck T and Hall MN  (1999) The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402(6762):689-92
18) Monteiro G and Netto LE  (2004) Glucose repression of PRX1 expression is mediated by Tor1p and Ras2p through inhibition of Msn2/4p in Saccharomyces cerevisiae. FEMS Microbiol Lett 241(2):221-8
19) Marion RM, et al.  (2004) Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression. Proc Natl Acad Sci U S A 101(40):14315-22
20) Martin DE, et al.  (2004) TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell 119(7):969-79
21) Dilova I, et al.  (2004) Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1.Rtg3p-dependent target genes. J Biol Chem 279(45):46527-35
22) Tate JJ, et al.  (2002) Mks1p is required for negative regulation of retrograde gene expression in Saccharomyces cerevisiae but does not affect nitrogen catabolite repression-sensitive gene expression. J Biol Chem 277(23):20477-82
23) Schmidt A, et al.  (1996) TOR2 is required for organization of the actin cytoskeleton in yeast. Proc Natl Acad Sci U S A 93(24):13780-5
24) deHart AK, et al.  (2003) Receptor internalization in yeast requires the Tor2-Rho1 signaling pathway. Mol Biol Cell 14(11):4676-84
25) Wullschleger S, et al.  (2005) Molecular organization of target of rapamycin complex 2. J Biol Chem 280(35):30697-704
26) Bjornsti MA and Houghton PJ  (2004) The TOR pathway: a target for cancer therapy. Nat Rev Cancer 4(5):335-48
27) Martin DE and Hall MN  (2005) The expanding TOR signaling network. Curr Opin Cell Biol 17(2):158-66