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Proteasome inhibitor MG ‐132 induces MCPIP 1 expression
Author(s) -
Skalniak Lukasz,
Koj Aleksander,
Jura Jolanta
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12264
Subject(s) - proteasome , proteasome inhibitor , downregulation and upregulation , p38 mitogen activated protein kinases , microbiology and biotechnology , hela , protein kinase a , kinase , chemistry , messenger rna , intracellular , protein degradation , biology , cell , gene , biochemistry
The proteasome is a protein complex responsible for the degradation of polyubiquitin‐tagged proteins. Besides the removal of target proteins, the proteasome also participates in the regulation of gene transcription in both proteolytic and non‐proteolytic fashion. In this study the effect of proteasome inhibition on the basal expression of monocyte chemotactic protein‐1 induced protein 1 ( MCPIP 1) was examined. Treatment of HepG2 or HeLa cells with proteasome inhibitor MG ‐132 resulted in a significant increase of MCPIP 1 expression, both at m RNA and protein level. Interestingly, MG ‐132 did not alter MCPIP 1 stability. Instead, the observed protein increase was blocked by actinomycin D , suggesting the involvement of de novo m RNA synthesis in the increase of MCPIP 1 protein following MG ‐132 treatment. Using several inhibitors we determined the participation of extracellular‐signal‐regulated kinase 1/2 and p38 kinases in MCPIP 1 upregulation by MG ‐132. Our findings show for the first time the impact of proteasome inhibition on MCPIP 1 protein expression by modulation of the activity of intracellular signaling pathways. Overexpression of MCPIP 1‐ myc protein decreased the viability of HeLa cells but not HepG2 cells, which correlates with the increased susceptibility of HeLa cells to MG‐132 toxicity. Notably, both MG ‐132 treatment and MCPIP 1‐ myc overexpression led to the activation of apoptosis, as revealed by the induction of caspases 3/7 in both types of cell lines. This suggests the involvement of MCPIP 1 upregulation in toxic properties of proteasome inhibition, which is an acknowledged approach to the treatment of several cancer types.