Characterization of an alternatively spliced GADD45α, GADD45α1 isoform, in arsenic-treated epithelial cells

✍ Scribed by Yadong Zhang; Kevin Beezhold; Vince Castranova; Xianglin Shi; Fei Chen

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 667 KB
• Volume: 48
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20483

✦ Synopsis

Abstract

A new GADD45α isoform, GADD45α1, was identified in the cellular response to arsenic. DNA sequencing and biochemical analyses suggested that GADD45α1 is derived from an alternative splicing of the GADD45α mRNA by skipping the region corresponding to exon2 of the gadd45α gene during mRNA maturation. In addition to the size difference due to the lack of 34 amino acids encoded by exon2, GADD45α1 and GADD45α proteins differ in their effects on cell proliferation and cell cycle transition. Unlike GADD45α, the GADD45α1 is unable to attenuate cell growth. In over‐expression experiments, the full length GADD45α, but not the GADD45α1, sensitized cells to arsenic‐induced prometaphase arrest of the cell cycle. Furthermore, GADD45α1 appears to be able to antagonize the function of the GADD45α on the G2/M phase cell cycle arrest as demonstrated in cotransfection experiment. Thus, these data suggest that the generation of the GADD45α1 isoform may not only offset but also antagonize the effects of arsenic and GADD45α on cell growth and cell cycle regulation. © 2008 Wiley‐Liss, Inc.