In a recent study, scientists from the Department of Biology at MIT discovered that the SIRT1 gene, which is associated with longer life span, may also be linked to a pathway that reduces the level of cholesterol in the body.
The researchers found that this gene activates a cellular pathway that flushes out cholesterol from the body using high density lipoprotein (HDL) or "good" cholesterol.
They showed that low SIRT1 levels in mice resulted in accumulation of cholesterol in cells such as macrophages. This was due to reduced activity of the liver X receptor (LXR) protein, which is responsible for transporting cholesterol out of macrophage cells. SIRT1 is a positive regulator of LXR as it promotes deacetylation and subsequent ubiquitination. Studies have also shown that loss of SIRT1 in vivo reduces the expression of a variety of LXR targets involved in lipid metabolism.
This discovery has great potential to enable researchers to design drugs that could lower the risk of diseases associated with high cholesterol, such as atherosclerosis and Alzheimer's disease.
SynaTate™, an application on the MGRC portal, can be used to analyse functional regions of this gene. In this case, SynaTate gave a high peak at position 1062-1172bp in the third forward reading frame. This peak had keywords which annotated it as a NAD-dependent. Searching this amino acid region against a SynaBASE of UniProtKB/Swiss-Prot Release 52.1 revealed homology to other NAD-dependent deacetylase from mouse and yeast. Hence, this 10bp domain could be an important functional domain common to other classes of deacetylases.