Pim-1 protein kinase is nuclear in Burkitt's lymphoma: Nuclear localization is necessary for its biologic effects

Yurij Ionov, Xuan Le, Brian J. Tunquist, John Sweetenham, Traci Sachs, John Ryder, Thomas Johnson, Michael B. Lilly, Andrew S. Kraft

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Background: The Pim-1 33-kDa protein is a serine/threonine protein kinase that is capable of enhancing the rate of occurrence of c-Myc-induced lymphomas, and functions to block factor-withdrawal and genotoxic stress-induced apoptosis. Materials and Methods: We used human lymphoma samples and tissue culture cells to examine the cellular location of this protein and its mechanism of action. Results: We found that Pim-1 can be located in the cytoplasm, the cytoplasm and nucleus, or the nucleus of cells of normal lymph nodes, but is only located in the nucleus in Burkitt's lymphoma cells. On transfection of Pim-1 into HeLa cells, a nuclear localization is observed that is not dependent upon kinase activity, but appears to be regulated by the carboxy terminal half of the protein. Because Pim-1 is known to regulate apoptosis and human Mdm2 (HDM2) contains a consensus Pim-1 phosphorylation site, the possible role of Pim-1 in modulating HDM2 was examined. When Pim-1 and HDM2 are transfected transiently into 293 cells, the presence of Pim-1 results in an increase in the levels of the HDM2 protein. This effect requires the presence of the entire HDM2 protein. Export of Pim-1 out of the nucleus by attachment of a nuclear export signal decreased its ability to regulate the levels of HDM2 protein. Conclusion: The nuclear location of Pim-1 is essential for its regulation of the levels of HDM2 protein, and possibly for additional biological activities of this protein kinase.

Original languageEnglish (US)
Pages (from-to)167-178
Number of pages12
JournalAnticancer Research
Volume23
Issue number1 A
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Burkitt's lymphoma
  • HDM2
  • Normal lymph node
  • Nuclear
  • Pim-1 protein kinase
  • Transcription

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ionov, Y., Le, X., Tunquist, B. J., Sweetenham, J., Sachs, T., Ryder, J., Johnson, T., Lilly, M. B., & Kraft, A. S. (2003). Pim-1 protein kinase is nuclear in Burkitt's lymphoma: Nuclear localization is necessary for its biologic effects. Anticancer Research, 23(1 A), 167-178.