We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

SIRT1 deacetylates and positively regulates the nuclear receptor LXR.

Molecular cell | Oct 12, 2007

The NAD(+)-dependent deacetylase Sir2 regulates life span in lower eukaryotes. The mammalian ortholog SIRT1 regulates physiological processes including apoptosis, fat metabolism, glucose homeostasis, and neurodegeneration. Here we show that SIRT1 is a positive regulator of liver X receptor (LXR) proteins, nuclear receptors that function as cholesterol sensors and regulate whole-body cholesterol and lipid homeostasis. LXR acetylation is evident at a single conserved lysine (K432 in LXRalpha and K433 in LXRbeta) adjacent to the ligand-regulated activation domain AF2. SIRT1 interacts with LXR and promotes deacetylation and subsequent ubiquitination. Mutations of K432 eliminate activation of LXRalpha by this sirtuin. Loss of SIRT1 in vivo reduces expression of a variety of LXR targets involved in lipid metabolism, including ABCA1, an ATP-binding cassette (ABC) transporter that mediates an early step of HDL biogenesis. Our findings suggest that deacetylation of LXRs by SIRT1 may be a mechanism that affects atherosclerosis and other aging-associated diseases.

Pubmed ID: 17936707 RIS Download

Mesh terms: Acetylation | Animals | Cell Line | Cholesterol | DNA-Binding Proteins | Gene Expression Regulation | Homeostasis | Humans | Hydrocarbons, Fluorinated | Lipid Metabolism | Liver | Liver X Receptors | Lysine | Mice | Mice, Knockout | Models, Molecular | Orphan Nuclear Receptors | Promoter Regions, Genetic | Protein Isoforms | Protein Structure, Tertiary | Receptors, Cytoplasmic and Nuclear | Sirtuin 1 | Sirtuins | Sulfonamides | Triglycerides | Ubiquitin

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

Associated grants


Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.