Deregulated cyclin E induces chromosome instability

Charles H. Spruck, Kwang-Ai Won and Steven I. Reed ()
Additional contact information
Charles H. Spruck: MB-7, The Scripps Research Institute
Kwang-Ai Won: MB-7, The Scripps Research Institute
Steven I. Reed: MB-7, The Scripps Research Institute

Nature, 1999, vol. 401, issue 6750, 297-300

Abstract: 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 phase1,2. However, in many human tumours cyclin E is overexpressed3 and the levels of protein and kinase activity are often deregulated relative to the cell cycle4,5,6,7. 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.

Date: 1999
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/45836 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:401:y:1999:i:6750:d:10.1038_45836

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/45836

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().