Cdc2-cyclin E complexes regulate the G1/S phase transition
Aleem, Eiman ; Kiyokawa, Hiroaki and Kaldis, Philipp LU
(2005)
In Nature Cell Biology
7(8).
p.831-836
- Abstract
The cyclin-dependent kinase inhibitor p27Kip1 is known as a negative regulator of cell-cycle progression and as a tumour suppressor. Cdk2 is the main target of p27 (refs 2, 3) and therefore we hypothesized that loss of Cdk2 activity should modify the p27-/- mouse phenotype. Here, we show that although p27-/- Cdk2-/- mice developed ovary tumours and tumours in the anterior lobe of the pituitary, we failed to detect any functional complementation in p27-/- Cdk2-/- double-knockout mice, indicating a parallel pathway regulated by p27. We observed elevated levels of S phase and mitosis in tissues of p27-/- Cdk2-/- mice concomitantly with elevated Cdc2... (More)
The cyclin-dependent kinase inhibitor p27Kip1 is known as a negative regulator of cell-cycle progression and as a tumour suppressor. Cdk2 is the main target of p27 (refs 2, 3) and therefore we hypothesized that loss of Cdk2 activity should modify the p27-/- mouse phenotype. Here, we show that although p27-/- Cdk2-/- mice developed ovary tumours and tumours in the anterior lobe of the pituitary, we failed to detect any functional complementation in p27-/- Cdk2-/- double-knockout mice, indicating a parallel pathway regulated by p27. We observed elevated levels of S phase and mitosis in tissues of p27-/- Cdk2-/- mice concomitantly with elevated Cdc2 activity in p27-/- Cdk2-/- extracts. p27 binds to Cdc2, cyclin B1, cyclin A2, or suc1 complexes in wild-type and Cdk2-/- extracts. In addition, cyclin E binds to and activates Cdc2. Our in vivo results provide strong evidence that Cdc2 may compensate the loss of Cdk2 function.
(Less)
- author
- Aleem, Eiman
; Kiyokawa, Hiroaki
and Kaldis, Philipp
LU
- publishing date
- 2005-08-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Cell Biology
- volume
- 7
- issue
- 8
- pages
- 6 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:16007079
- scopus:23144451917
- ISSN
- 1465-7392
- DOI
- 10.1038/ncb1284
- language
- English
- LU publication?
- no
- id
- fce41f92-6a06-4fe3-aa67-60ad866ab4a8
- date added to LUP
- 2019-09-18 14:26:27
- date last changed
- 2025-05-16 13:29:08
@article{fce41f92-6a06-4fe3-aa67-60ad866ab4a8,
abstract = {{<p>The cyclin-dependent kinase inhibitor p27<sup>Kip1</sup> is known as a negative regulator of cell-cycle progression and as a tumour suppressor. Cdk2 is the main target of p27 (refs 2, 3) and therefore we hypothesized that loss of Cdk2 activity should modify the p27<sup>-/-</sup> mouse phenotype. Here, we show that although p27<sup>-/-</sup> Cdk2<sup>-/-</sup> mice developed ovary tumours and tumours in the anterior lobe of the pituitary, we failed to detect any functional complementation in p27<sup>-/-</sup> Cdk2<sup>-/-</sup> double-knockout mice, indicating a parallel pathway regulated by p27. We observed elevated levels of S phase and mitosis in tissues of p27<sup>-/-</sup> Cdk2<sup>-/-</sup> mice concomitantly with elevated Cdc2 activity in p27<sup>-/-</sup> Cdk2<sup>-/-</sup> extracts. p27 binds to Cdc2, cyclin B1, cyclin A2, or suc1 complexes in wild-type and Cdk2<sup>-/-</sup> extracts. In addition, cyclin E binds to and activates Cdc2. Our in vivo results provide strong evidence that Cdc2 may compensate the loss of Cdk2 function.</p>}},
author = {{Aleem, Eiman and Kiyokawa, Hiroaki and Kaldis, Philipp}},
issn = {{1465-7392}},
language = {{eng}},
month = {{08}},
number = {{8}},
pages = {{831--836}},
publisher = {{Nature Publishing Group}},
series = {{Nature Cell Biology}},
title = {{Cdc2-cyclin E complexes regulate the G1/S phase transition}},
url = {{http://dx.doi.org/10.1038/ncb1284}},
doi = {{10.1038/ncb1284}},
volume = {{7}},
year = {{2005}},
}