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

• Published in: Leukemia research 2006-02, Vol.30 (2), p.153-163
• Main Authors: Qi, Chen-Feng, Xiang, Shao, Shin, Min Sun, Hao, Xingpei, Lee, Chang Hoon, Zhou, Jeff X., Torrey, Ted A., Hartley, Janet W., Fredrickson, Torgny N., Morse, Herbert C.
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Cell-cycle regulation; 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; Mouse B cell lymphoma; p27; Phosphorylation; Proto-Oncogene Proteins c-akt - analysis; RNA, Messenger - analysis
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2005.06.025

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.