Jacobs Journal of Genetics

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

*Samira Zohra MIDOUN
Department Of Genetics And Developmental Biology, Huazhong University Of Science And Technology, China

*Corresponding Author:
Samira Zohra MIDOUN
Department Of Genetics And Developmental Biology, Huazhong University Of Science And Technology, China
Email:lhong@mail.hust.edu.cn

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

Introduction

UBIAD1 (a.k.a TERE1, Transitional Epithelium Response gene 1), a tumor-suppressor gene, has been for the first time screened and characterized by its distinct expression level between normal human tissues and transformed Transitional Cell Carcinoma (TCC) [1]. The gene is ubiquitously expressed in various normal human tissues but mainly manifested in the bladder mucosa, where TERE1 was ab initio discovered in, from which comes the occurrence of its appellation as the Transitional Epithelium Response gene 1 (TERE1). TERE1 gene mapped to chromosome 1p36.11-1p36.33 locus [1], was designated as a center of putative tumor suppressor genes for distinct tumor cell populations [2-4]. Published reports have depicted an estimated division of UBIAD1 between Golgi, ER and mitochondria [5-7]. The subcellular localization varies according to the type of cells and might be disturbed in tumor cells. This disruption may dysregulate the adequate function of the protein. UBIAD1 protein has a prenyltransferase activity [8], principally responsible for vitamin K2 and CoQ10 biosynthesis [5, 6]. Interestingly, intracellular homeostasis of both cholesterol and vitamin K relies on the function of apoE, which besides being one of UBIAD1 substrates, is also an important LXR target gene [9, 10]. Besides, UBIAD1 protein has a binding affinity with HMG CoA reductase [11]. Geranylgeraniol can prevent this binding, inducing reductase degradation and consequently an intracellular cholesterol regulation [12]. It is believed that UBIAD1 enzyme and its product K2 are potential regulators of the intracellular elevated cholesterol amount, a common phenotype encountered in distinct cancer cells and in SCD (Schnyder Corneal Dystrophy) cases [8,13].