How cells remove HMG-CoA synthase 1, a key enzyme for making cholesterol-related molecules
Mechanism and Significance of HMG Co-A Synthase 1 Degradation
This project explains how cells break down HMG-CoA synthase 1—a key enzyme for cholesterol and isoprenoid production—when growth signals change, which could point to new anti-cancer strategies for people with cancer.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Sloan-Kettering Inst Can Research NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11308720 on NIH RePORTER |
What this research studies
Researchers at Memorial Sloan Kettering will study how the enzyme HMG-CoA synthase 1 (HMGCS1), which helps make cholesterol and related molecules, is removed inside cells when growth signals change. They will use degradomics and biochemical methods to measure how quickly HMGCS1 is broken down when the mTORC1 growth pathway is turned off and to identify the specific E3 ubiquitin ligase that tags HMGCS1 for destruction. Most experiments will be done in cells and laboratory assays to map the molecular steps controlling HMGCS1 stability. The team will test how changing these pathways alters cancer-relevant cell behavior to identify possible drug targets.
Who could benefit from this research
Good fit: Patients whose tumors show high mTORC1 activity or dependence on the mevalonate/cholesterol pathway (for example some breast, prostate, or myeloma cases) would be most relevant to therapies that could emerge from this work.
Not a fit: People without cancer or patients whose tumors are not driven by mTORC1 activation or the mevalonate pathway are unlikely to benefit directly from this research.
Why it matters
Potential benefit: If successful, this work could reveal new targets to block cancer cells from making molecules they need to grow, guiding future anti-cancer drug development.
How similar studies have performed: Drugs that affect the mevalonate pathway (like statins) and proteasome inhibitors have shown effects in cancer, but targeting HMGCS1 degradation via a specific E3 ligase is a newer, less-tested approach.
Where this research is happening
New York, United States
- Sloan-Kettering Inst Can Research — New York, United States (Active)
Researchers
- Principal investigator: An, Heeseon — Sloan-Kettering Inst Can Research
- Study coordinator: An, Heeseon
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.