Yeast sterol regulatory element-binding protein (SREBP) cleavage requires Cdc48 and Dsc5, a ubiquitin regulatory X domain-containing subunit of the Golgi Dsc E3 ligase

J Biol Chem. 2012 Jan 2;287(1):672-81. doi: 10.1074/jbc.M111.317370. Epub 2011 Nov 15.

Abstract

Schizosaccharomyces pombe Sre1 is a membrane-bound transcription factor that controls adaptation to hypoxia. Like its mammalian homolog, sterol regulatory element-binding protein (SREBP), Sre1 activation requires release from the membrane. However, in fission yeast, this release occurs through a strikingly different mechanism that requires the Golgi Dsc E3 ubiquitin ligase complex and the proteasome. The mechanistic details of Sre1 cleavage, including the link between the Dsc E3 ligase complex and proteasome, are not well understood. Here, we present results of a genetic selection designed to identify additional components required for Sre1 cleavage. From the selection, we identified two new components of the fission yeast SREBP pathway: Dsc5 and Cdc48. The AAA (ATPase associated with diverse cellular activities) ATPase Cdc48 and Dsc5, a ubiquitin regulatory X domain-containing protein, interact with known Dsc complex components and are required for SREBP cleavage. These findings provide a mechanistic link between the Dsc E3 ligase complex and the proteasome in SREBP cleavage and add to a growing list of similarities between the Dsc E3 ligase and membrane E3 ligases involved in endoplasmic reticulum-associated degradation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mutagenesis
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism*
  • Proteolysis
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sterol Regulatory Element Binding Proteins / metabolism*
  • Ubiquitin-Protein Ligases / chemistry*
  • Valosin Containing Protein

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Dsc5 protein, S pombe
  • Membrane Proteins
  • Protein Subunits
  • Schizosaccharomyces pombe Proteins
  • Sre1 protein, S pombe
  • Sterol Regulatory Element Binding Proteins
  • Ubiquitin-Protein Ligases
  • Adenosine Triphosphatases
  • Valosin Containing Protein