Deregulated cyclin E induces chromosome instability View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-09

AUTHORS

Charles H. Spruck, Kwang-Ai Won, Steven I. Reed

ABSTRACT

Cyclin E, a regulatory subunit of cyclin-dependent kinase 2 (Cdk2), is an important regulator of entry into S phase in the mammalian cell cycle. In normal dividing cells, cyclin E accumulates at the G1/S-phase boundary and is degraded as cells progress through S phase. However, in many human tumours cyclin E is overexpressed and the levels of protein and kinase activity are often deregulated relative to the cell cycle. It is not understood how alterations in expression of cyclin E contribute to tumorigenesis. Here we show that constitutive cyclin-E overexpression in both immortalized rat embryo fibroblasts and human breast epithelial cells results in chromosome instability (CIN). In contrast, analogous expression of cyclin D1 or A does not increase the frequency of CIN. Cyclin-E-expressing cells that exhibit CIN have normal centrosome numbers. However, constitutive overexpression of cyclin E impairs S-phase progression, indicating that aberrant regulation of this process may be responsible for the CIN observed. These results indicate that downregulation of cyclin-E/Cdk2 kinase activity following the G1/S-phase transition may be necessary for the maintenance of karyotypic stability. More... »

PAGES

297

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/45836

DOI

http://dx.doi.org/10.1038/45836

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1005965021

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10499591


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