Identification of Rbd2 as a candidate protease for sterol regulatory element binding protein (SREBP) cleavage in fission yeast
| Autor: | Dong-Uk Kim, Jinsil Kim, Sook-Jeong Lee, Sujin Kim, Hye-jeong Ha, Ah-Reum Choi, Kwang Lae Hoe |
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| Rok vydání: | 2015 |
| Předmět: |
Proteases
Saccharomyces cerevisiae Proteins Biophysics Cleavage (embryo) Biochemistry Substrate Specificity symbols.namesake Schizosaccharomyces Molecular Biology Transcription factor Cell Proliferation Sterol Regulatory Element Binding Proteins Binding Sites biology Cell Biology Golgi apparatus biology.organism_classification Sterol regulatory element-binding protein Ubiquitin ligase Enzyme Activation Oxygen Oxidative Stress Schizosaccharomyces pombe symbols biology.protein Peptide Hydrolases Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications. 468:606-610 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2015.10.165 |
| Popis: | Lipid homeostasis in mammalian cells is regulated by sterol regulatory element-binding protein (SREBP) transcription factors that are activated through sequential cleavage by Golgi Site-1 and Site-2 proteases. Fission yeast SREBP, Sre1, engages a different mechanism involving the Golgi Dsc E3 ligase complex, but it is not clearly understood exactly how Sre1 is proteolytically cleaved and activated. In this study, we screened the Schizosaccharomyces pombe non-essential haploid deletion collection to identify missing components of the Sre1 cleavage machinery. Our screen identified an additional component of the SREBP pathway required for Sre1 proteolysis named rhomboid protein 2 (Rbd2). We show that an rbd2 deletion mutant fails to grow under hypoxic and hypoxia-mimetic conditions due to lack of Sre1 activity and that this growth phenotype is rescued by Sre1N, a cleaved active form of Sre1. We found that the growth inhibition phenotype under low oxygen conditions is specific to the strain with deletion of rbd2, not any other fission yeast rhomboid-encoding genes. Our study also identified conserved residues of Rbd2 that are required for Sre1 proteolytic cleavage. All together, our results suggest that Rbd2 is a functional SREBP protease with conserved residues required for Sre1 cleavage and provide an important piece of the puzzle to understand the mechanisms for Sre1 activation and the regulation of various biological and pathological processes involving SREBPs. |
| Databáze: | OpenAIRE |
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