US EPA

1519038 

Journal Article 

The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues 

Kurooka, H; Sugai, M; Mori, K; Yokota, Y 

2013 

Yes 

Biochemical and Biophysical Research Communications
ISSN: 0006-291X
EISSN: 1090-2104 

Elsevier 

433 

4 

579-585 

English 

23523789 

10.1016/j.bbrc.2013.03.027 

WOS:000318259100039 

https://linkinghub.elsevier.com/retrieve/pii/S0006291X13004427
Exit
 

Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite. 

Id3; Transcriptional repressor; NES; Arsenite; Cysteine