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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

Cell Death Dis. 2018; 
Xu Z, Duan F, Lu H, Abdulkadhim Dragh M, Xia Y, Liang H, Hong L
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Recombinant Proteins The following antibodies were used in this study: p-cRaf (Ser259) (#9421), p-c-Raf (Ser338) (#9427), p-c-Raf (Ser289/296/301) (#9431), c-Raf (#9422), p-ERK1/2 (#4370), total-ERK1/2 (#4695), and caspase-3 (#9662) from Cell Signaling Technology (USA); anti-phosphoMEK (Ser218/222)/MEK2 (Ser222/226) (#2283379) from Millipore (USA); MEK1/2 (Ab-217/221) (#21203) antibody from Signalway Antibody (USA); Antibodies detecting actin (A01010-1) and GAPDH (A01020-1) from Abbkine (USA); Flag tag monoclonal antibody (A00187) from GenScript (China); GFP tag antibody (#66002-1) and HMGB1 (#10829-1) from proteintech (China); 488/549/ 645-conjugated secondary antibody from Abbkine (USA); HRP-conjugated secondary antibody from ABGENT (USA); UBIAD1 antibody (ab36832), Pan-Ras antibody (ab16907), and LC3B (AB192890) from Abcam (USA); rabbit IgG, mouse IgG from Immunoreagents (USA). Antibodies used for experiments with Drosophila were as follows: p-ERK (sc-7976) and ERK2 (sc-153) from Santa Cruz (US), pan-Ras (#3339) from Cell Signaling Technology (USA). HEIX antibodies were synthesized by GL Biochem (Shanghai, China), as previously described19 Get A Quote

摘要

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 ... More

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