ArticleThe Journal of biological chemistry2009
Geranylgeranyl pyrophosphate is a potent regulator of HRD-dependent 3-Hydroxy-3-methylglutaryl-CoA reductase degradation in yeast.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Triazole Stress Induces Accelerated Degradation ofbioRxiv : the preprint server for biology · 2026Article
- Farnesol and geranylgeraniol in plant reproduction: insights from Arabidopsis and beyond.Journal of experimental botany · 2026Review
- The Mevalonate Pathway: Innovations, Applications, and Challenges in Biotechnology with Emphasis on Fungal Biology.Journal of fungi (Basel, Switzerland) · 2026Review
- The potential of metabolic engineering for sustainable phytosterol production.Advanced biotechnology · 2026Review
- Rab geranylgeranyl transferase activity is required for proper sterol biosynthesis in Arabidopsis thaliana.Plant & cell physiology · 2026Article
- Chromosome-level genome assembly ofHorticulture research · 2026Article
- Competition between Der1 and ERAD-M substrates controls Hrd1 complex function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Direct binding to sterols accelerates endoplasmic reticulum-associated degradation of HMG CoA reductase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Exploring the "misfolding problem" by systematic discovery and analysis of functional-but-degraded proteins.Molecular biology of the cell · 2023Article
- PeakDecoder enables machine learning-based metabolite annotation and accurate profiling in multidimensional mass spectrometry measurements.Nature communications · 2023Article
- An ERAD-independent role for rhomboid pseudoprotease Dfm1 in mediating sphingolipid homeostasis.The EMBO journal · 2023Article
- Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogenPeerJ · 2023Article
- Post-Translational Regulation of HMG CoA Reductase.Cold Spring Harbor perspectives in biology · 2022Review
- Endoplasmic reticulum-related E3 ubiquitin ligases: Key regulators of plant growth and stress responses.Plant communications · 2021Review
- Inner-nuclear-membrane-associated degradation employs Dfm1-independent retrotranslocation and alleviates misfolded transmembrane-protein toxicity.Molecular biology of the cell · 2021Article
- The Heat Shock Protein 40-Type Chaperone MASH Supports the Endoplasmic Reticulum-Associated Degradation E3 Ubiquitin Ligase MAKIBISHI1 inFrontiers in plant science · 2021Article
- Combinatorial Metabolic Engineering inBioengineering (Basel, Switzerland) · 2020Article
- Assays for protein retrotranslocation in ERAD.Methods in enzymology · 2019Article
- Mallostery: Filling a niche between quality and metabolic control.The Journal of biological chemistry · 2018Article
- "Mallostery"-ligand-dependent protein misfolding enables physiological regulation by ERAD.The Journal of biological chemistry · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGR), the rate-limiting enzymes of sterol synthesis, undergoes feedback-regulated endoplasmic reticulum degradation in both mammals and yeast. The yeast Hmg2p isozyme is subject to ubiquitin-mediated endoplasmic reticulum degradation by the HRD pathway. We had previously shown that alterations in cellular levels of the 15-carbon sterol pathway intermediate farnesyl pyrophosphate (FPP) cause increased Hmg2p ubiquitination and degradation. We now present evidence that the FPP-derived, 20-carbon molecule geranylgeranyl pyrophosphate (GGPP) is a potent endogenous regulator of Hmg2p degradation. This work was launched by the unexpected observation that GGPP addition directly to living yeast cultures caused high potency and specific stimulation of Hmg2p degradation. This effect of GGPP was not recapitulated by FPP, GGOH, or related isoprenoids. GGPP-caused Hmg2p degradation met all the criteria for the previously characterized endogenous signal. The action of added GGPP did not require production of endogenous sterol molecules, indicating that it did not act by causing the build-up of an endogenous pathway signal. Manipulation of endogenous GGPP by several means showed that naturally made GGPP controls Hmg2p stability. Analysis of the action of GGPP indicated that the molecule works upstream of retrotranslocation and can directly alter the structure of Hmg2p. We propose that GGPP is the FPP-derived regulator of Hmg2p ubiquitination. Intriguingly, the sterol-dependent degradation of mammalian HMGR is similarly stimulated by the addition of GGOH to intact cells, implying that a dependence on 20-carbon geranylgeranyl signals may be a common conserved feature of HMGR regulation that may lead to highly specific therapeutic approaches for modulation of HMGR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.