Expression of the cyclin-dependent kinase inhibitor p27 and its deregulation in mouse B cell lymphomas

Leuk Res. 2006 Feb;30(2):153-63. doi: 10.1016/j.leukres.2005.06.025. Epub 2005 Aug 24.

Abstract

CDKN1B (p27) regulates cell-cycle progression at the G1-S transition by suppressing the cyclin E/CDK2 kinase complex. In normal lymphocytes and most human B cell non-Hodgkin lymphomas (NHL), there is an inverse correlation between proliferative activity and expression of p27; however, a subset of NHL with high mitotic indices expresses p27, which is inactive due to sequestration in nuclear protein complexes or due to cytoplasmic retention. Our studies of mouse B cell NHL also identified cases with high proliferative activity and high levels of p27 at a surprisingly high frequency. Here, p27 was complexed with D-type cyclins 1 and 3 and with the COPS9 protein, JAB1. In addition, we found cytoplasmic sequestration following phosphorylation by activated AKT.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cyclin D1 / analysis
  • Cyclin D3
  • Cyclin E / analysis
  • Cyclin-Dependent Kinase Inhibitor p27 / analysis*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Cyclins / analysis
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lymphoma, B-Cell / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / analysis
  • RNA, Messenger / analysis

Substances

  • CCND3 protein, human
  • Ccnd3 protein, mouse
  • Cyclin D3
  • Cyclin E
  • Cyclins
  • Ki-67 Antigen
  • RNA, Messenger
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Proto-Oncogene Proteins c-akt