Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

J. Ma, H. K. Arnold, M. B. Lilly, R. C. Sears, Andrew Kraft

Research output: Contribution to journalArticle

54 Citations (Scopus)

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, ε 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.

Original languageEnglish (US)
Pages (from-to)5145-5153
Number of pages9
JournalOncogene
Volume26
Issue number35
DOIs
StatePublished - Aug 2 2007
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-pim-1
Protein-Serine-Threonine Kinases
Protein Kinases
Peptidylprolyl Isomerase
Polyomavirus Transforming Antigens
Protein Phosphatase 2
Okadaic Acid
Viral Tumor Antigens
Small Interfering RNA
Proteolysis
Half-Life
Lymphoma
Catalytic Domain
Proteins

Keywords

  • B56β
  • Pim-1
  • Pin1
  • PP2A
  • Protein kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A. / Ma, J.; Arnold, H. K.; Lilly, M. B.; Sears, R. C.; Kraft, Andrew.

In: Oncogene, Vol. 26, No. 35, 02.08.2007, p. 5145-5153.

Research output: Contribution to journalArticle

Ma, J. ; Arnold, H. K. ; Lilly, M. B. ; Sears, R. C. ; Kraft, Andrew. / Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A. In: Oncogene. 2007 ; Vol. 26, No. 35. pp. 5145-5153.
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