Yeast SREBP Cleavage Activation Requires the Golgi Dsc E3 Ligase Complex

Emerson V. Stewart, Christine C. Nwosu, Zongtian Tong, Assen Roguev, Timothy D. Cummins, Dong Uk Kim, Jacqueline Hayles, Han Oh Park, Kwang Lae Hoe, David W. Powell, Nevan J. Krogan, Peter J. Espenshade

Research output: Contribution to journalArticle

Abstract

Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. Here we report that while SREBP function is conserved in fungi, fission yeast employs a different mechanism for SREBP cleavage. Using genetics and biochemistry, we identified four genes defective for SREBP cleavage, dsc1-4, encoding components of a transmembrane Golgi E3 ligase complex with structural homology to the Hrd1 E3 ligase complex involved in endoplasmic reticulum-associated degradation. The Dsc complex binds SREBP and cleavage requires components of the ubiquitin-proteasome pathway: the E2-conjugating enzyme Ubc4, the Dsc1 RING E3 ligase, and the proteasome. dsc mutants display conserved aggravating genetic interactions with components of the multivesicular body pathway in fission yeast and budding yeast, which lacks SREBP. Together, these data suggest that the Golgi Dsc E3 ligase complex functions in a post-ER pathway for protein degradation.

Original languageEnglish (US)
Pages (from-to)160-171
Number of pages12
JournalMolecular cell
Volume42
Issue number2
DOIs
StatePublished - Apr 22 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Stewart, E. V., Nwosu, C. C., Tong, Z., Roguev, A., Cummins, T. D., Kim, D. U., Hayles, J., Park, H. O., Hoe, K. L., Powell, D. W., Krogan, N. J., & Espenshade, P. J. (2011). Yeast SREBP Cleavage Activation Requires the Golgi Dsc E3 Ligase Complex. Molecular cell, 42(2), 160-171. https://doi.org/10.1016/j.molcel.2011.02.035