Cadmium interferes with the degradation of ATF5 via a post-ubiquitination step of the proteasome degradation pathway
| Autor: | Yuji Takahashi, Tamotsu Nishida, Yusuke Hiwatashi, Shigeru Takahashi, Hiroyuki Uekusa, Takuya Akimoto, Mihoko Namimatsu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Proteasome Endopeptidase Complex
Arsenites Biophysics chemistry.chemical_element Biology CREB Biochemistry Epitope Ubiquitin Cadmium Chloride Chlorocebus aethiops Animals Humans Nuclear export signal Molecular Biology Transcription factor Cadmium Protein Stability Ubiquitination Cell Biology Fusion protein Activating Transcription Factors Cell biology Protein Structure Tertiary Proteasome chemistry COS Cells biology.protein Proteasome Inhibitors |
| Zdroj: | Biochemical and biophysical research communications. 380(3) |
| ISSN: | 1090-2104 |
| Popis: | ATF5 is a member of the CREB/ATF family of transcription factors. In the current study, using a transient transfection system to express FLAG epitope fusion proteins of ATF5, we have shown that CdCl{sub 2} or NaAsO{sub 3} increases the protein levels of ATF5 in cells, and that cadmium stabilizes the ATF5 protein. Proteasome inhibitors had a similar effect to cadmium on the cellular accumulation of ATF5. Proteasome inhibition led to an increase in ubiquitinated ATF5, while cadmium did not appear to reduce the extent of ATF5 ubiquitination. ATF5 contains a putative nuclear export signal within its N-terminus. We demonstrated that whereas deletion of N-terminal region resulted in a increase of ATF5 levels, this region does not appear to be involved in the ubiquitination of ATF5. These results indicate that ATF5 is targeted for degradation by the ubiquitin-proteasome pathway, and that cadmium slows the rate of ATF5 degradation via a post-ubiquitination mechanism. |
| Databáze: | OpenAIRE |
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