The role of p27 in controlling the oxygen-dependent checkpoint of mammalian cells in late G1.
We have studied hypoxia-induced cell cycle arrest in human cells where the retinoblastoma tumour suppressor protein (pRb) is either functional (T-47D cells) or abrogated by expression of the HPV18 E7 oncoprotein (NHIK 3025 cells). Cells of both types are arrested in a restriction point in late G1, here denoted as the oxygen-dependent restriction point in late G1. This arrest seems to occur under extreme hypoxia in all types of mammalian cells so far tested. During an 18-h exposure to extreme hypoxia, the p27 protein level increased in G1-phase in both cells lines investigated and was followed by a binding between p27 and CDK2. This was observed both in the pRb-positive T-47D cells and in the pRb-negative NHIK 3025 cells. We, therefore, believe that p27 and not pRb is the mediator of this oxygen-dependent checkpoint in late G1. Our results also suggest that p27 regulates the restart of cell cycle progression of these arrested cells after reoxygenation.
Graff
Pål
P
Department of Physics, The Biophysics Group, University of Oslo, P.O. Box 1048 Blindern, 0316 Oslo, Norway. p_graff@yahoo.com
Amellem
Oystein
O
Seim
Jo
J
Stokke
Trond
T
Pettersen
Erik O
EO
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D042846:CDC2-CDC28 Kinases / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D018797:Cell Cycle Proteins; D019927:Cyclin E; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D010100:Oxygen