Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Kinase-independent function of Cyclin E

Geng, Yan ; Lee, Young Mi ; Welcker, Markus ; Swanger, Jherek ; Zagozdzon, Agnieszka ; Winer, Joel D. ; Roberts, James M. ; Kaldis, Philipp LU orcid ; Clurman, Bruce E. and Sicinski, Piotr (2007) In Molecular Cell 25(1). p.127-139
Abstract

E-type cyclins are thought to drive cell-cycle progression by activating cyclin-dependent kinases, primarily CDK2. We previously found that cyclin E-null cells failed to incorporate MCM helicase into DNA prereplication complex during G0 → S phase progression. We now report that a kinase-deficient cyclin E mutant can partially restore MCM loading and S phase entry in cyclin E-null cells. We found that cyclin E is loaded onto chromatin during G0 → S progression. In the absence of cyclin E, CDT1 is normally loaded onto chromatin, whereas MCM is not, indicating that cyclin E acts between CDT1 and MCM loading. We observed a physical association of cyclin E with CDT1 and with MCMs. We propose that cyclin E facilitates... (More)

E-type cyclins are thought to drive cell-cycle progression by activating cyclin-dependent kinases, primarily CDK2. We previously found that cyclin E-null cells failed to incorporate MCM helicase into DNA prereplication complex during G0 → S phase progression. We now report that a kinase-deficient cyclin E mutant can partially restore MCM loading and S phase entry in cyclin E-null cells. We found that cyclin E is loaded onto chromatin during G0 → S progression. In the absence of cyclin E, CDT1 is normally loaded onto chromatin, whereas MCM is not, indicating that cyclin E acts between CDT1 and MCM loading. We observed a physical association of cyclin E with CDT1 and with MCMs. We propose that cyclin E facilitates MCM loading in a kinase-independent fashion, through physical interaction with CDT1 and MCM. Our work indicates that-in addition to their function as CDK activators-E cyclins play kinase-independent functions in cell-cycle progression.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
CELLCYCLE, SIGNALING
in
Molecular Cell
volume
25
issue
1
pages
127 - 139
publisher
Cell Press
external identifiers
  • scopus:33846018073
  • pmid:17218276
ISSN
1097-2765
DOI
10.1016/j.molcel.2006.11.029
language
English
LU publication?
no
id
986916b7-6050-4c1f-ba87-762fc1441370
date added to LUP
2019-09-18 14:18:42
date last changed
2024-04-30 21:51:53
@article{986916b7-6050-4c1f-ba87-762fc1441370,
  abstract     = {{<p>E-type cyclins are thought to drive cell-cycle progression by activating cyclin-dependent kinases, primarily CDK2. We previously found that cyclin E-null cells failed to incorporate MCM helicase into DNA prereplication complex during G<sub>0</sub> → S phase progression. We now report that a kinase-deficient cyclin E mutant can partially restore MCM loading and S phase entry in cyclin E-null cells. We found that cyclin E is loaded onto chromatin during G<sub>0</sub> → S progression. In the absence of cyclin E, CDT1 is normally loaded onto chromatin, whereas MCM is not, indicating that cyclin E acts between CDT1 and MCM loading. We observed a physical association of cyclin E with CDT1 and with MCMs. We propose that cyclin E facilitates MCM loading in a kinase-independent fashion, through physical interaction with CDT1 and MCM. Our work indicates that-in addition to their function as CDK activators-E cyclins play kinase-independent functions in cell-cycle progression.</p>}},
  author       = {{Geng, Yan and Lee, Young Mi and Welcker, Markus and Swanger, Jherek and Zagozdzon, Agnieszka and Winer, Joel D. and Roberts, James M. and Kaldis, Philipp and Clurman, Bruce E. and Sicinski, Piotr}},
  issn         = {{1097-2765}},
  keywords     = {{CELLCYCLE; SIGNALING}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{127--139}},
  publisher    = {{Cell Press}},
  series       = {{Molecular Cell}},
  title        = {{Kinase-independent function of Cyclin E}},
  url          = {{http://dx.doi.org/10.1016/j.molcel.2006.11.029}},
  doi          = {{10.1016/j.molcel.2006.11.029}},
  volume       = {{25}},
  year         = {{2007}},
}