Characterization of an N-terminally truncated cyclin A isoform in mammalian cells.
Cyclin A is essential for regulating key transitions in the eukaryotic cell cycle including initiation of DNA replication and mitosis. This paper describes the characterization of a truncated cyclin A isoform (cyclin A(t)) in vitro in cultured mammalian cells and in mouse tissues. The presence of cyclin A(t) in specific cell types correlates with the ability of cell extracts to cleave in vitro translated cyclin A. In CHO-K1 cells, cyclin A processing to cyclin A(t) occurs at the N terminus; it does not involve the 26 S proteasome, nor could it be induced by conditional overexpression of the cyclin-dependent kinase inhibitor p27(Kip1). However, high cell densities lead to increased cyclin A(t) levels. Unlike full-length cyclin A, cyclin A(t) localizes to the cytoplasm, where it binds Cdk2. The data suggest that cyclin A processing occurs in vivo to yield an N-terminally truncated isoform by an unknown mechanism that is regulated by cell density. Differential subcellular localization may provide the first insights into the physiological role of cyclin A(t).
Kaufmann
H
H
Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Hönggerberg HPT, CH-8093 Zurich, Switzerland.
Marone
R
R
Olayioye
M A
MA
Bailey
J E
JE
Fussenegger
M
M
D000818:Animals; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002460:Cell Line; D006224:Cricetinae; D019925:Cyclin A / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D011233:Precipitin Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D019925:Cyclin A; D020033:Protein Isoforms; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases