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

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.

Abbreviations: APCT, anaplastic plasmacytoma, B-CLL, B cell chronic lymphocytic leukæmia/lymphoma, BL, burkitt lymphoma, BLL, burkitt-like lymphoma, CBL, centroblastic DLBCL, CDK, cyclin-dependent kinase, CKI, CDK inhibitor, DLBCL, diffuse large B cell lymphoma, FBL, follicular B cell lymphoma, IBL, immunoblastic DLBCL, MALT, mucosal associated lymphoid tissue, MM, multiple myeloma, MZL, marginal zone lymphoma, NHL, non-Hodgkin lymphoma, SBL, small B cell lymphoma, SDS-PAGE, sodium dodecylsulfate polyacrylamide gel electrophoresis

Keywords: p27, Mouse B cell lymphoma, Cell-cycle regulation