Arsenic trioxide targets MTHFD1 and SUMO-dependent nuclear de novo thymidylate biosynthesis

Abstract excerpt

Significance We have identified de novo thymidylate biosynthesis as a target of arsenic at exposure levels observed in human populations. Arsenic enhances methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) small ubiquitin-like modifier (SUMO)-ylation and subsequent proteolytic degradation of MTHFD1 and serine hydroxymethyltransferase (SHMT), resulting in depressed rates of de novo thymidylate synthesis, elevated...

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