Vitamin K2 Prevents Lymphoma in Drosophila

Dragh, Maytham A.; Zhou, Xu; Al-Allak, Zainab S.; Li, Hong

doi:10.1038/s41598-017-17270-9

Cited by 16 publications

(7 citation statements)

References 63 publications

(81 reference statements)

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“…Loss of function of heix or gain of function of Ras leads to an increased proliferation of hemocytes 19 , 45 . Hemocyte proliferation is closely correlated with the formation of melanotic mass, which can be attributed to an increase in the number of crystal cells associated with melanization 65 , 66 . Our study show that heix mutant leads to activation of Ras signaling on the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it is reported that the melanotic mass formation in Drosophila is linked to a hemocyte-mediated immune response 64 . Previous studies report that loss of heix function not only activates the Ras signaling pathway but also leads to the activation of immune-related pathways (Toll, JAK/STAT, IMD pathways) 19 , 66 . Therefore, besides the Ras pathway, the formation of melanotic mass in heix mutants may be influenced by immune-related pathways.…”

Section: Discussionmentioning

confidence: 99%

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UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras

Zhou

Duan

et al. 2018

Cell Death Dis

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UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a key role in biosynthesis of vitamin K2 and coenzyme Q10 using geranylgeranyl diphosphate (GGPP). However, the mechanism by which UBIAD1 participates in tumorigenesis remains unknown. This study show that UBIAD1 interacts with H-Ras, retains H-Ras in the Golgi apparatus, prevents H-Ras trafficking from the Golgi apparatus to the plasma membrane, blocks the aberrant activation of Ras/MAPK signaling, and inhibits the proliferation of bladder cancer cells. In addition, GGPP was required to maintain the function of UBIAD1 in regulating the Ras/ERK signaling pathway. A Drosophila model was employed to confirm the function of UBIAD1/HEIX in vivo. The activation of Ras/ERK signaling at the plasma membrane induced melanotic masses in Drosophila larvae. Our study suggests that UBIAD1 serves as a tumor suppressor in cancer and tentatively reveals the underlying mechanism of melanotic mass formation in Drosophila.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras

Zhou

Duan

et al. 2018

Cell Death Dis

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“…Additionally, a synergy between vitamin D and vitamin K was necessary, thus necessitating the administration of vitamin K in severe COVID-19 patients prior to vitamin D supplementation [ 141 ]. Vitamin K was reported to have positive impacts in most cases of cancer and autoimmune diseases, which has been previously studied and reviewed [ 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 ] and is summarized in Figure 5 . The emerging roles of vitamin K1 and K3 have also been noted due to the notable effects induced by this subclass of vitamins in regulation of tyrosine kinases and their downstream oncogenic pathways, as well as their regulatory effect on certain transcription factors [ 159 ].…”

Section: Impact Of Fat-soluble Vitamins In Covid-19 Prevention and Tr...mentioning

confidence: 99%

Evaluating Risk: Benefit Ratio of Fat-Soluble Vitamin Supplementation to SARS-CoV-2-Infected Autoimmune and Cancer Patients: Do Vitamin–Drug Interactions Exist?

Mekky

Elemam

Eltahtawy

et al. 2022

Life

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COVID-19 is a recent pandemic that mandated the scientific society to provide effective evidence-based therapeutic approaches for the prevention and treatment for such a global threat, especially to those patients who hold a higher risk of infection and complications, such as patients with autoimmune diseases and cancer. Recent research has examined the role of various fat-soluble vitamins (vitamins A, D, E, and K) in reducing the severity of COVID-19 infection. Studies showed that deficiency in fat-soluble vitamins abrogates the immune system, thus rendering individuals more susceptible to COVID-19 infection. Moreover, another line of evidence showed that supplementation of fat-soluble vitamins during the course of infection enhances the viral clearance episode by promoting an adequate immune response. However, more thorough research is needed to define the adequate use of vitamin supplements in cancer and autoimmune patients infected with COVID-19. Moreover, it is crucial to highlight the vitamin–drug interactions of the COVID-19 therapeutic modalities and fat-soluble vitamins. With an emphasis on cancer and autoimmune patients, the current review aims to clarify the role of fat-soluble vitamins in SARS-CoV-2 infection and to estimate the risk-to-benefit ratio of a fat-soluble supplement administered to patients taking FDA-approved COVID-19 medications such as antivirals, anti-inflammatory, receptor blockers, and monoclonal antibodies.

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“…Heix (Heixuedian), is an orthologous protein of UBIAD1 in Drosophila melanogaster , composed of 359 amino acids with a molecular weight of 39.22 kDa ( 42 ). Following Heix mutation, a black dot phenotype lymphoma appeared in the 3rd to 4th instar larvae in Drosophila ( 49 , 50 ). UBIAD1 localizes at the mitochondria and converts vitamin K 1 to K 2 , which is a significant cofactor in eukaryotic blood coagulation and an electronic carrier binding to the cell membrane in bacteria ( 43 ).…”

Section: Subcellular Localization and Functions Of Ubiad1mentioning

confidence: 99%

Functional study of SCCD pathogenic gene UBIAD1 (Review)

Xie

2021

Mol Med Rep

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Schnyder's crystalline corneal dystrophy (SCCD) is a rare autosomal dominant genetic disorder that is characterized by progressive corneal opacity, owing to aberrant accumulation of cholesterol and phospholipids in the cornea. A number of SCCD affected families have been reported in the world since 1924, when it was first described. In 2007, the molecular basis of SCCD was demonstrated to be associated with a tumor suppressor, UbiA prenyltransferase domain-containing 1 (UBIAD1), which was isolated from the bladder mucosa and demonstrated to be involved in vitamin K 2 and CoQ10 biosynthesis. This sterol triggers the binding of UBIAD1 to 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) at endoplasmic reticulum (ER) membranes, which is regulated by an intracellular geranylgeranyl diphosphate (GGpp) molecule. The inability of SCCD-associated UBIAD1 to bind GGpp results in the consistent binding of UBIAD1 to HMGCR at ER membranes. This binding leads to HMGCRs being redundant. Therefore, they cannot be degraded through ER-associated degradation to synthesize abundant cholesterol in tissue cells. Excess corneal cholesterol accumulation thus leads to SCCD disease. After decades, the efforts of numerous ophthalmologists and scientists have helped clarify the molecular basis and pathogenesis of SCCD, which has guided the effective diagnosis and treatment of this genetic disorder. However, more studies need to be conducted to understand the pathogenesis of SCCD disease from a genetic basis by studying the defective gene, UBIAD1. Results would guide effective diagnosis and treatment of the inherited eye disease.

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Vitamin K2 Prevents Lymphoma in Drosophila

Cited by 16 publications

References 63 publications

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras

Evaluating Risk: Benefit Ratio of Fat-Soluble Vitamin Supplementation to SARS-CoV-2-Infected Autoimmune and Cancer Patients: Do Vitamin–Drug Interactions Exist?

Functional study of SCCD pathogenic gene UBIAD1 (Review)

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