p27 is regulated independently of Skp2 in the absence of Cdk2

Cyclin-dependent kinase 2 (Cdk2) is dispensable for mitotic cell cycle progression and Cdk2 knockout mice are viable due to the compensatory functions of other Cdks. In order to assess the role of Cdk2 under limiting conditions, we used Skp2 knockout mice that exhibit increased levels of Cdk inhibit...

Full description

Saved in:
Bibliographic Details
Main Authors: Kaldis, Philipp, Kotoshiba, Shuhei, Gopinathan, Lakshmi, Pfeiffenberger, Elisabeth, Rahim, Anisa, Vardy, Leah Karen Anne, Nakayama, Keiko, Nakayama, Keiichi I.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2016
Subjects:
Online Access:https://hdl.handle.net/10356/81991
http://hdl.handle.net/10220/41082
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-81991
record_format dspace
spelling sg-ntu-dr.10356-819912022-02-16T16:27:41Z p27 is regulated independently of Skp2 in the absence of Cdk2 Kaldis, Philipp Kotoshiba, Shuhei Gopinathan, Lakshmi Pfeiffenberger, Elisabeth Rahim, Anisa Vardy, Leah Karen Anne Nakayama, Keiko Nakayama, Keiichi I. School of Biological Sciences Cyclin-dependent kinase Knockout mice Cyclin-dependent kinase 2 (Cdk2) is dispensable for mitotic cell cycle progression and Cdk2 knockout mice are viable due to the compensatory functions of other Cdks. In order to assess the role of Cdk2 under limiting conditions, we used Skp2 knockout mice that exhibit increased levels of Cdk inhibitor, p27Kip1, which is able to inhibit Cdk2 and Cdk1. Knockdown of Cdk2 abrogated proliferation of Skp2−/− mouse embryonic fibroblasts, encouraging us to generate Cdk2−/−Skp2−/− double knockout mice. Cdk2−/−Skp2−/− double knockout mice are viable and display similar phenotypes as Cdk2−/− and Skp2−/− mice. Unexpectedly, fibroblasts generated from Cdk2−/−Skp2−/− double knockout mice proliferated at normal rates. The increased stability of p27 observed in Skp2−/− MEFs was not observed in Cdk2−/−Skp2−/− double knockout fibroblasts indicating that in the absence of Cdk2, p27 is regulated by Skp2-independent mechanisms. Ablation of other ubiquitin ligases for p27 such as KPC1, DDB1, and Pirh2 did not restore stability of p27 in Cdk2−/−Skp2−/− MEFs. Our findings point towards novel and alternate pathways for p27 regulation. ASTAR (Agency for Sci., Tech. and Research, S’pore) 2016-08-04T09:27:08Z 2019-12-06T14:44:22Z 2016-08-04T09:27:08Z 2019-12-06T14:44:22Z 2014 Journal Article Kotoshiba, S., Gopinathan, L., Pfeiffenberger, E., Rahim, A., Vardy, L. A., Nakayama, K. I., et al. (2014). p27 is regulated independently of Skp2 in the absence of Cdk2. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1843(2), 436-445. 0167-4889 https://hdl.handle.net/10356/81991 http://hdl.handle.net/10220/41082 10.1016/j.bbamcr.2013.11.005 24269842 en Biochimica et Biophysica Acta (BBA) - Molecular Cell Research © 2013 Elsevier B.V. 10 p.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Cyclin-dependent kinase
Knockout mice
spellingShingle Cyclin-dependent kinase
Knockout mice
Kaldis, Philipp
Kotoshiba, Shuhei
Gopinathan, Lakshmi
Pfeiffenberger, Elisabeth
Rahim, Anisa
Vardy, Leah Karen Anne
Nakayama, Keiko
Nakayama, Keiichi I.
p27 is regulated independently of Skp2 in the absence of Cdk2
description Cyclin-dependent kinase 2 (Cdk2) is dispensable for mitotic cell cycle progression and Cdk2 knockout mice are viable due to the compensatory functions of other Cdks. In order to assess the role of Cdk2 under limiting conditions, we used Skp2 knockout mice that exhibit increased levels of Cdk inhibitor, p27Kip1, which is able to inhibit Cdk2 and Cdk1. Knockdown of Cdk2 abrogated proliferation of Skp2−/− mouse embryonic fibroblasts, encouraging us to generate Cdk2−/−Skp2−/− double knockout mice. Cdk2−/−Skp2−/− double knockout mice are viable and display similar phenotypes as Cdk2−/− and Skp2−/− mice. Unexpectedly, fibroblasts generated from Cdk2−/−Skp2−/− double knockout mice proliferated at normal rates. The increased stability of p27 observed in Skp2−/− MEFs was not observed in Cdk2−/−Skp2−/− double knockout fibroblasts indicating that in the absence of Cdk2, p27 is regulated by Skp2-independent mechanisms. Ablation of other ubiquitin ligases for p27 such as KPC1, DDB1, and Pirh2 did not restore stability of p27 in Cdk2−/−Skp2−/− MEFs. Our findings point towards novel and alternate pathways for p27 regulation.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Kaldis, Philipp
Kotoshiba, Shuhei
Gopinathan, Lakshmi
Pfeiffenberger, Elisabeth
Rahim, Anisa
Vardy, Leah Karen Anne
Nakayama, Keiko
Nakayama, Keiichi I.
format Article
author Kaldis, Philipp
Kotoshiba, Shuhei
Gopinathan, Lakshmi
Pfeiffenberger, Elisabeth
Rahim, Anisa
Vardy, Leah Karen Anne
Nakayama, Keiko
Nakayama, Keiichi I.
author_sort Kaldis, Philipp
title p27 is regulated independently of Skp2 in the absence of Cdk2
title_short p27 is regulated independently of Skp2 in the absence of Cdk2
title_full p27 is regulated independently of Skp2 in the absence of Cdk2
title_fullStr p27 is regulated independently of Skp2 in the absence of Cdk2
title_full_unstemmed p27 is regulated independently of Skp2 in the absence of Cdk2
title_sort p27 is regulated independently of skp2 in the absence of cdk2
publishDate 2016
url https://hdl.handle.net/10356/81991
http://hdl.handle.net/10220/41082
_version_ 1725985771190484992