Dynamic changes in p27kip1 variant expression in activated lymphocytes.
The p27Kip1 cell cycle inhibitor (p27) has emerged as a critical mediator of normal cellular growth control. We report the expression of a 24 kD C-terminal variant of p27 in normal peripheral blood lymphocytes. This variant is rapidly degraded in a proteasome-dependent manner when lymphocytes are activated by interleukin-2 or by superantigen. Whereas p24 degradation is complete within 16 h of mitogen addition, full-length p27 is decreased only modestly over 72 h of mitogen exposure and is present in activated and cycling lymphocytes. Persistent p27 is present in a complex with cyclin D3 in activated lymphocytes, and is localized both in the nucleus and cytoplasm. These results indicate that lymphocytes exiting from quiescence use several mechanisms to overcome the p27Kip1-enforced cell cycle checkpoint, and that elimination of p27 is not required for cell cycle entry.
Yaroslavskiy
B
B
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Watkins
S C
SC
Alber
S
S
Steinman
R A
RA
D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D056743:Cyclin D3; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism; D003546:Cysteine Endopeptidases; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D005312:Fetal Blood / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009124:Muscle Proteins; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D020033:Protein Isoforms; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D014470:Umbilical Cord / Q000378:metabolism
C534696:CCND3 protein, human; C534697:Ccnd3 protein, mouse; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D016213:Cyclins; D008840:Microfilament Proteins; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D020033:Protein Isoforms; C058992:Tagln protein, mouse; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex