Stimulation of Akt Poly-Ubiquitination and Proteasomal Degradation in P388D1 Cells by 7-Ketocholesterol and 25-Hydroxycholesterol
Document Type
Article
Publication Date
7-1-2009
Description
Akt plays a role in protecting macrophages from apoptosis induced by some oxysterols. Previously we observed enhanced degradation of Akt in P388D1 moncocyte/macrophages following treatment with 25-hydroxycholesterol (25-OH) or 7-ketocholesterol (7-KC). In the present report we examine the role of the ubiquitin proteasomal pathway in this process. We show that treatment with 25-OH or 7-KC results in the accumulation of poly-ubiquitinated Akt, an effect that is enhanced by co-treatment with the proteasome inhibitor MG-132. Modification of Akt by the addition of a Gly-Ala repeat (GAr), a domain known to block ubiquitin-dependent targeting of proteins to the proteasome, resulted in a chimeric protein that is resistant to turn-over induced by 25-OH or 7-KC and provides protection from apoptosis induced by these oxysterols. These results uncover a new aspect of oxysterol regulation of Akt in macrophages; oxysterol-stimulated poly-ubiquitination of Akt and degradation by the proteasomal pathway.
Citation Information
Liu, June; Netherland, Courtney; Pickle, Theresa; Sinensky, Michael S.; and Thewke, Douglas P.. 2009. Stimulation of Akt Poly-Ubiquitination and Proteasomal Degradation in P388D1 Cells by 7-Ketocholesterol and 25-Hydroxycholesterol. Archives of Biochemistry and Biophysics. Vol.487(1). 54-58. https://doi.org/10.1016/j.abb.2009.05.004 PMID: 19464253 ISSN: 0003-9861