Skp1 forms multiple protein complexes, including RAVE, a regulator of V-ATPase assembly

Nat Cell Biol. 2001 Apr;3(4):384-91. doi: 10.1038/35070067.

Abstract

SCF ubiquitin ligases are composed of Skp1, Cdc53, Hrt1 and one member of a large family of substrate receptors known as F-box proteins (FBPs). Here we report the identification, using sequential rounds of epitope tagging, affinity purification and mass spectrometry, of 16 Skp1 and Cdc53-associated proteins in budding yeast, including all components of SCF, 9 FBPs, Yjr033 (Rav1) and Ydr202 (Rav2). Rav1, Rav2 and Skp1 form a complex that we have named 'regulator of the (H+)-ATPase of the vacuolar and endosomal membranes' (RAVE), which associates with the V1 domain of the vacuolar membrane (H+)-ATPase (V-ATPase). V-ATPases are conserved throughout eukaryotes, and have been implicated in tumour metastasis and multidrug resistance, and here we show that RAVE promotes glucose-triggered assembly of the V-ATPase holoenzyme. Previous systematic genome-wide two-hybrid screens yielded 17 proteins that interact with Skp1 and Cdc53, only 3 of which overlap with those reported here. Thus, our results provide a distinct view of the interactions that link proteins into a comprehensive cellular network.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cullin Proteins*
  • Cytoplasm / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Glucose / metabolism
  • Holoenzymes / metabolism
  • Proton-Translocating ATPases / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • S-Phase Kinase-Associated Proteins
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Vacuolar Proton-Translocating ATPases*

Substances

  • Cdc53 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cullin Proteins
  • Fungal Proteins
  • Holoenzymes
  • Recombinant Fusion Proteins
  • S-Phase Kinase-Associated Proteins
  • Saccharomyces cerevisiae Proteins
  • Vacuolar Proton-Translocating ATPases
  • Proton-Translocating ATPases
  • Glucose