TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway

Mol Cell. 2001 Nov;8(5):1017-26. doi: 10.1016/s1097-2765(01)00386-0.

Abstract

In Saccharomyces cerevisiae, the rapamycin-sensitive TOR kinases negatively regulate the type 2A-related phosphatase SIT4 by promoting the association of this phosphatase with the inhibitor TAP42. Here, we describe TIP41, a conserved TAP42-interacting protein involved in the regulation of SIT4. Deletion of the TIP41 gene confers rapamycin resistance, suppresses a tap42 mutation, and prevents dissociation of SIT4 from TAP42. Furthermore, a TIP41 deletion prevents SIT4-dependent events such as dephosphorylation of the kinase NPR1 and nuclear translocation of the transcription factor GLN3. Thus, TIP41 negatively regulates the TOR pathway by binding and inhibiting TAP42. The binding of TIP41 to TAP42 is stimulated upon rapamycin treatment via SIT4-dependent dephosphorylation of TIP41, suggesting that TIP41 is part of a feedback loop that rapidly amplifies SIT4 phosphatase activity under TOR-inactivating conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antifungal Agents / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Fungal
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins*
  • Phosphatidylinositol 3-Kinases*
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Phosphatase 2
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins*
  • Ribonucleoprotein, U2 Small Nuclear / metabolism
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction / physiology*
  • Sirolimus / pharmacology
  • Transcription Factors / metabolism
  • Two-Hybrid System Techniques

Substances

  • Adaptor Proteins, Signal Transducing
  • Antifungal Agents
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • GLN3 protein, S cerevisiae
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Ribonucleoprotein, U2 Small Nuclear
  • SAP155 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • TAP42 protein, S cerevisiae
  • TIP41 protein, S cerevisiae
  • Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR1 protein, S cerevisiae
  • TOR2 protein, S cerevisiae
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • SIT4 protein, S cerevisiae
  • Sirolimus