model as a guide, a variety of biochemical approaches are being
utilized to 1) reveal the mechanism for sterol-sensing in Phase
I of the HMG CoA reductase degradative pathway, and 2) define
Phase II of the pathway through identification of molecules recruited
to the HMG CoA reductase-Insig complex in the presence of sterols.
In addition, we are also embarking upon a genetic analysis of
HMG CoA reductase degradation in somatic cells by selecting for
mutant cells incapable of accelerating degradation of the enzyme.
The inability of the mutant cells to accelerate degradation of
HMG CoA reductase forms the basis for their selection. Once obtained,
the defective gene that confers the HMG CoA reductase degradation-deficient
phenotype will be identified through genetic complementation and
expression cloning techniques.