Association of Cdk2/cyclin E and NF-kappa B complexes at G1/S phase.
NF-kappa B/Rel family plays a pivotal role in a wide variety of cellular functions including growth, development, apoptosis and stress responses. Recent studies indicated that NF-kappa B is also involved in the cell cycle regulation, and high expression of c-Rel results in a cell cycle arrest at the G1/S-phase transition (Bash, J., Zong, W,-X., and Gelinas, C. (1997) Mol. Cell. Biol. 17, 6526-6536). Here we report the detection of Cdk2, a critical kinase responsible for the G1/S-phase transition, in immune complexes precipitated by the NF-kappa B antisera. Cdk2 and NF-kappa B association was detected by co-precipitation in the nuclear lysates of the G1/S-phase cells, and was found in cultured cell lines and in T cells purified from human peripheral blood. Using an affinity column containing the C-terminal peptide of human c-Rel, we isolated cyclin E, the regulatory subunit of the Cdk2 complex, as a c-Rel-binding protein. These findings support and provide physical basis for the involvement of NF-kappa B in the G1/S-phase cell cycle control, and suggest an important role played by the C-terminal sequence of c-Rel.
Chen
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Intramural Research Support Program, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Li
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D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001665:Binding Sites; D042846:CDC2-CDC28 Kinases; D002460:Cell Line; D002846:Chromatography, Affinity; D019927:Cyclin E / Q000737:chemistry / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D016196:S Phase / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
D019927:Cyclin E; D046911:Macromolecular Substances; D016328:NF-kappa B; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases