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  2. 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

  • Cell Death Dis. 2018 Dec 5;9(12):1170. doi: 10.1038/s41419-018-1215-4.
Zhiliang Xu 1 Fengsen Duan 1 Huiai Lu 1 Maytham Abdulkadhim Dragh 1 Yanzhi Xia 1 Huageng Liang 2 Ling Hong 3
Affiliations

Affiliations

  • 1 Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
  • 2 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
  • 3 Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. lhong@mail.hust.edu.cn.
Abstract

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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