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Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA.
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findings suggest that the high expression of ALKBH8 is critical for the growth and progression of bladder cancer
Many euk (show ALKBH Antibodies)aryotic tRNAs contain the wobble modification 5-m (show MCM5 Antibodies)ethoxycarbonylmethyl-uridine (mcm5U). It is demonstrated that (R)- and (S)-5-methoxycarbonylhydroxymethyluridine (mchm5U), hydroxylated forms of mcm(5)U, are present in mammalian tRNA-Arg(UCG), and tRNA-Gly(UCC), respectively. It is shown that the hydroxylation reaction leading to the formation of (S)-mchm5U is catalyzed by the oxygenase (AlkB) domain of ALKBH8.
The methyltransferase domain of ALKBH8 is demonstrated to be a functional homologue of the Saccharomyces cerevisiae Trm9 protein, mediating the last step in the formation of the wobble uridine modification 5-methoxycarbonylmethyl-uridine in tRNA. This modification is shown to be important for efficient selenoprotein synthesis. ALKBH8 knock-out mice are generated and described.
Data show that human AlkB (show ALKBH Antibodies) homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm(5 (show MCM5 Antibodies))U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival.
Findings indicate a role for ALKBH8 in urothelial carcinoma cell survival mediated by NOX-1 (show NOX1 Antibodies)-dependent ROS (show ROS1 Antibodies) signals, further suggesting therapeutic strategies in human bladder cancer by inducing JNK (show MAPK8 Antibodies)/p38 (show CRK Antibodies)/gammaH2AX (show H2AFX Antibodies)-mediated cell death by silencing of ALKBH8.
Alkbh8 and tRNA modifications as central regulators of cellular oxidative stress responses in mammalian systems.
The AlkB (show ALKBH Antibodies) domain of ALKBH8 specifically hydroxylates mcm(5 (show MCM5 Antibodies))U into (S)-mchm(5)U in tRNA-Gly(UCC).
Data show that ALKBH8 is a tRNA methyltransferase required for the final step in the biogenesis of mcm5U.
Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA. Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA. Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys). Required for normal survival after DNA damage. May inhibit apoptosis and promote cell survival and angiogenesis (By similarity).
AlkB homologue 8
, S-adenosyl-L-methionine-dependent tRNA methyltransferase ABH8
, alkylated DNA repair protein alkB homolog 8
, probable alpha-ketoglutarate-dependent dioxygenase ABH8
, tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ABH8