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- Title
Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A.
- Authors
Ma, J.; Arnold, H. K.; Lilly, M. B.; Sears, R. C.; Kraft, A. S.
- Abstract
The Pim protein kinases are serine threonine protein kinases that regulate important cellular signaling pathway molecules, and enhance the ability of c-Myc to induce lymphomas. We demonstrate that a cascade of events controls the cellular levels of Pim. We find that overexpression of the protein phosphatase (PP) 2A catalytic subunit decreases the activity and protein levels of Pim-1. This effect is reversed by the application of okadaic acid, an inhibitor of PP2A, and is blocked by SV40 small T antigen that is known to disrupt B subunit binding to PP2A A and C subunits. Pim-1 can coimmunoprecipitate with the PP2A regulatory B subunit, B56β, but not B56α, γ, δ, ɛ or B55α. Using short hairpin RNA targeted at B56β, we demonstrate that decreasing the level of B56β increases the half-life of Pim-1 from 0.7 to 2.8 h, and decreases the ubiquitinylation level of Pim-1. We also find that Pin1, a prolyl-isomerase, is capable of binding Pim-1 and leads to a decrease in the protein level of Pim-1. On the basis of these observations, we hypothesize that phosphorylated Pim-1 binds Pin1 allowing the interaction of PP2A through B56β. Dephosphorylation of Pim-1 then allows for ubiquitinylation and protein degradation of Pim-1.Oncogene (2007) 26, 5145–5153; doi:10.1038/sj.onc.1210323; published online 12 February 2007
- Subjects
PROTEIN kinases; PHOSPHOTRANSFERASES; CYCLIN-dependent kinases; ISOMERASES; RNA; NUCLEIC acids
- Publication
Oncogene, 2007, Vol 26, Issue 35, p5145
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1210323