Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Cdk2 and Cdk4 cooperatively control the expression of Cdc2

Berthet, Cyril and Kaldis, Philipp LU orcid (2006) In Cell Division 1.
Abstract

Progression through the mammalian cell cycle is associated with the activity of four cyclin dependent kinases (Cdc2/Cdk1, Cdk2, Cdk4, and Cdk6). Knockout mouse models have provided insight into the interplay of these Cdks. Most of these models do not exhibit major cell cycle defects revealing redundancies, and suggesting that a single Cdk might be sufficient to drive the cell cycle, similar as in yeast. Recent work on Cdk2/Cdk4 double knockouts has indicated that these two Cdks are required to phosphorylate Rb during late embryogenesis. The lack of Rb phosphorylation is progressive and associated with reduced E2F-inducible gene expression. Cdk2 and Cdk4 share the essential function of coupling the G1/S transition with mitosis. However,... (More)

Progression through the mammalian cell cycle is associated with the activity of four cyclin dependent kinases (Cdc2/Cdk1, Cdk2, Cdk4, and Cdk6). Knockout mouse models have provided insight into the interplay of these Cdks. Most of these models do not exhibit major cell cycle defects revealing redundancies, and suggesting that a single Cdk might be sufficient to drive the cell cycle, similar as in yeast. Recent work on Cdk2/Cdk4 double knockouts has indicated that these two Cdks are required to phosphorylate Rb during late embryogenesis. The lack of Rb phosphorylation is progressive and associated with reduced E2F-inducible gene expression. Cdk2 and Cdk4 share the essential function of coupling the G1/S transition with mitosis. However, proliferation in early embryogenesis appears to be independent of Cdk2 and Cdk4. We discuss these observations and propose molecular mechanisms that establish the requirement for Cdk2 and Cdk4 at the G1/S transition. We are considering that the balance between proliferation and differentiation is disturbed, which affects especially heart development and leads to embryonic lethality in Cdk2-/-Cdk4-/- mutants. We also discuss the specific functions of Cdk4 and Cdk6, which ironically do not compensate for each other.

(Less)
Please use this url to cite or link to this publication:
author
and
publishing date
type
Contribution to journal
publication status
published
in
Cell Division
volume
1
article number
10
publisher
BioMed Central (BMC)
external identifiers
  • scopus:34248395609
DOI
10.1186/1747-1028-1-10
language
English
LU publication?
no
id
be89b3de-453f-413f-8b0a-6be68cef348b
date added to LUP
2019-09-18 14:19:07
date last changed
2022-04-10 21:29:15
@article{be89b3de-453f-413f-8b0a-6be68cef348b,
  abstract     = {{<p>Progression through the mammalian cell cycle is associated with the activity of four cyclin dependent kinases (Cdc2/Cdk1, Cdk2, Cdk4, and Cdk6). Knockout mouse models have provided insight into the interplay of these Cdks. Most of these models do not exhibit major cell cycle defects revealing redundancies, and suggesting that a single Cdk might be sufficient to drive the cell cycle, similar as in yeast. Recent work on Cdk2/Cdk4 double knockouts has indicated that these two Cdks are required to phosphorylate Rb during late embryogenesis. The lack of Rb phosphorylation is progressive and associated with reduced E2F-inducible gene expression. Cdk2 and Cdk4 share the essential function of coupling the G1/S transition with mitosis. However, proliferation in early embryogenesis appears to be independent of Cdk2 and Cdk4. We discuss these observations and propose molecular mechanisms that establish the requirement for Cdk2 and Cdk4 at the G1/S transition. We are considering that the balance between proliferation and differentiation is disturbed, which affects especially heart development and leads to embryonic lethality in Cdk2<sup>-/-</sup>Cdk4<sup>-/-</sup> mutants. We also discuss the specific functions of Cdk4 and Cdk6, which ironically do not compensate for each other.</p>}},
  author       = {{Berthet, Cyril and Kaldis, Philipp}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Cell Division}},
  title        = {{Cdk2 and Cdk4 cooperatively control the expression of Cdc2}},
  url          = {{http://dx.doi.org/10.1186/1747-1028-1-10}},
  doi          = {{10.1186/1747-1028-1-10}},
  volume       = {{1}},
  year         = {{2006}},
}