The mammalian cholesterol synthesis enzyme squalene monooxygenase is proteasomally truncated to a constitutively active form.

ABSTRACT: Squalene monooxygenase (SM, also known as squalene epoxidase) is a rate-limiting enzyme of cholesterol synthesis that converts squalene to monooxidosqualene and is oncogenic in numerous cancer types. SM is subject to feedback regulation via cholesterol-induced proteasomal degradation, which depends on its lipid-sensing N-terminal regulatory domain. We previously identified an endogenous truncated form of SM with a similar abundance to full-length SM, but whether this truncated form is functional or subject to the same regulatory mechanisms as full-length SM is not known. Here, we show that truncated SM differs from full-length SM in two major ways: it is cholesterol resistant and adopts a peripheral rather than integral association with the endoplasmic reticulum membrane. However, truncate

SUBMITTER: Coates HW 

PROVIDER: S-EPMC8166775 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature