Jacobs Journal of Genetics

UBIAD1, a Prenyltransferase Enzyme Modulates Biological Functions Required for the Intracellular Homeostasis Maintenance

Published on: 2018-11-14

Abstract

Ever since a human version of Drosophila heixuedian (heix) has been identified as a tumor suppressor protein, a pertinent literature got deep interest to the human UBIAD1 protein, in terms to further evaluate the occurred molecular mechanism driving its function in human beings. Ubiad1 is a gene ubiquitously expressed in normal human tissues. The protein harbors a prenyltransferase functional domain conserved throughout the evolution. Under specific conditions, UBIAD1 participates in HMGCoA reductase degradation, thus preventing intracellular cholesterol accumulation. Cholesterol aggregation in the cornea is one of the fundamental reasons that causes SCD (Schnyder Corneal Dystrophy), a genetic disorder associated to defective UBIAD1 function. SCD mutations or loss of UBIAD1 lead to cancer progression by disrupting the process of UBIAD1/menaquinone-mediated cholesterol regulatory network. Interestingly, UBIAD1-reductase complex formation decides for the sub-localization of this prenyltransferase enzyme at ER levels or at Golgi membranes (after translocation). The profound effect of human UBIAD1 enzyme not only relies on its ability to synthesize menaquinone-4 (MK-4, vitamin K2) but also in the synthesis of CoQ10 (coenzyme Q10). Vitamin K2 serves as an electron carrier that rescues mitochondrial dysfunction in Drosophila and prevents mutated Pink-1-assoiated Parkinson’s disease. In addition, this vitamin effectively initiates apoptosis in various types of tumors through a caspase-dependent pathway. In another hand, UBIAD1 is crucial for cardiovascular protection function based on its role in CoQ10 biosynthesis. Taken together, UBIAD1 is a gene with multi-functions that spreads its effect to maintain intracellular homeostasis.

Keywords

Ubiad1; Vitamin K2; Coq10, Tumor; Scd; Parkinson’s Disease; Cholesterol; Cardiovascular Disease; CoQ10; SCD