Zinc deficiency causes neural tube defects through attenuation of p53 ubiquitylation.

ABSTRACT: Micronutrition is essential for neural tube closure, and zinc deficiency is associated with human neural tube defects. Here, we modeled zinc deficiency in mouse embryos, and used live imaging and molecular studies to determine how zinc deficiency affects neural tube closure. Embryos cultured with the zinc chelator TPEN failed to close the neural tube and showed excess apoptosis. TPEN-induced p53 protein stabilization in vivo and in neuroepithelial cell cultures and apoptosis was dependent on p53. Mechanistically, zinc deficiency resulted in disrupted interaction between p53 and the zinc-dependent E3 ubiquitin ligase Mdm2, and greatly reduced p53 ubiquitylation. Overexpression of human CHIP, a zinc-independent E3 ubiquitin ligase that targets p53, relieved TPEN-induced p53 stabilizat

SUBMITTER: Li H 

PROVIDER: S-EPMC6307889 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature