School of Medicine
The present study shows that arsenic induces GADD45α (growth arrest and DNA damage inducible gene 45α) mainly through post-transcriptional mechanism. Treatment of the human bronchial epithelial cell line, BEAS-2B, with arsenic(III) chloride (As 3+ ) resulted in a significant increase in GADD45α protein and mRNA. However, As 3+ only exhibited a marginal effect on the transcription of the GADD45α gene. The accumulation of GADD45α mRNA is largely achieved by the stabilization of GADD45α mRNA in the cellular response to As 3+ . As 3+ is able to induce binding of mRNA stabilizing proteins, nucleolin and less potently, HuR, to the GADD45α mRNA. Although As 3+ was unable to affect the expression of nucleolin, treatment of the cells with As 3+ resulted in re-distribution of nucleolin from nucleoli to nucleoplasm. Silencing of the nucleolin mRNA by RNA interference reversed As 3+ -induced stabilization of the GADD45α mRNA and accumulation of the GADD45α protein. Stabilization of GADD45α mRNA, thus, represents a novel mechanism contributing to the production of GADD45α and cell cycle arrest in response to As 3+ .
Digital Commons Citation
Zhang, Yadong; Bhatia, Deepak; Xia, Hongfeng; Castranova, Vince; Shi, Xianglin; and Chen, Fei, "Nucleolin links to arsenic-induced stabilization of GADD45α mRNA" (2006). Faculty & Staff Scholarship. 2871.
Zhang, Y. (2006). Nucleolin links to arsenic-induced stabilization of GADD45 mRNA. Nucleic Acids Research, 34(2), 485–495. https://doi.org/10.1093/nar/gkj459