Expression of the cyclin-dependent kinase inhibitor p27 and its deregulation in mouse B cell lymphomas.
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.
Qi
Chen-Feng
CF
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, Twinbrook I, Room 1421, National Institutes of Health, Rockville, MD, USA.
Xiang
Shao
S
Shin
Min Sun
MS
Hao
Xingpei
X
Lee
Chang Hoon
CH
Zhou
Jeff X
JX
Torrey
Ted A
TA
Hartley
Janet W
JW
Fredrickson
Torgny N
TN
Morse
Herbert C
HC
D000818:Animals; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000032:analysis; D056743:Cyclin D3; D019927:Cyclin E / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000032:analysis; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis
C534696:CCND3 protein, human; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D019927:Cyclin E; D016213:Cyclins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt