Related Experiment Video
Updated: Sep 21, 2026

Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
NS1- and minute virus of mice-induced cell cycle arrest: involvement of p53 and p21(cip1)
A Op De Beeck1, J Sobczak-Thepot, H Sirma
1Unité Hépatite C, CNRS-FRE 2369, Institut de Biologie de Lille et Institut Pasteur de Lille, 59021 Lille cedex, France. anne.op-de-beeck@ibl.fr
Abstract:
The nonstructural protein NS1 of the autonomous parvovirus minute virus of mice (MVMp) is cytolytic when expressed in transformed cells. Before causing extensive cell lysis, NS1 induces a multistep cell cycle arrest in G(1), S, and G(2), well reproducing the arrest in S and G(2) observed upon MVMp infection. In this work we investigated the molecular mechanisms of growth inhibition mediated by NS1 and MVMp. We show that NS1-mediated cell cycle arrest correlates with the accumulation of the cyclin-dependent kinase (Cdk) inhibitor p21(cip1) associated with both the cyclin A/Cdk and cyclin E/Cdk2 complexes but in the absence of accumulation of p53, a potent transcriptional activator of p21(cip1). By comparison, MVMp infection induced the accumulation of both p53 and p21(cip1). We demonstrate that p53 plays an essential role in the MVMp-induced cell cycle arrest in both S and G(2) by using p53 wild-type (+/+) and null (-/-) cells. Furthermore, only the G(2) arrest was abrogated in p21(cip1) null (-/-) cells. Together these results show that the MVMp-induced cell cycle arrest in S is p53 dependent but p21(cip1) independent, whereas the arrest in G(2) depends on both p53 and its downstream effector p21(cip1). They also suggest that induction of p21(cip1) by the viral protein NS1 arrests cells in G(2) through inhibition of cyclin A-dependent kinase activity.
Insights
The minute virus of mice (MVMp) nonstructural protein NS1 causes cell cycle arrest by accumulating p21(cip1), while MVMp infection relies on p53 and p21(cip1) for G2 arrest, revealing distinct mechanisms of viral growth inhibition.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- The minute virus of mice (MVMp) nonstructural protein NS1 is cytolytic and induces cell cycle arrest.
- NS1 expression mimics MVMp infection-induced cell cycle arrest in S and G2 phases.
- Understanding the molecular mechanisms of NS1 and MVMp-mediated growth inhibition is crucial.
Purpose of the Study:
- To investigate the molecular mechanisms of cell cycle arrest induced by NS1 and MVMp.
- To elucidate the roles of p53 and p21(cip1) in MVMp-induced cell cycle regulation.
Main Methods:
- Analyzing cell cycle arrest in G1, S, and G2 phases upon NS1 expression.
- Assessing the accumulation of p53 and p21(cip1) in NS1-expressing and MVMp-infected cells.
- Utilizing p53 wild-type and null cells, as well as p21(cip1) null cells to determine the roles of these proteins.
Main Results:
- NS1-mediated cell cycle arrest correlates with p21(cip1) accumulation, independent of p53.
- MVMp infection induces cell cycle arrest in S and G2, dependent on both p53 and p21(cip1).
- The S phase arrest is p53-dependent but p21(cip1)-independent, while G2 arrest requires both p53 and p21(cip1).
Conclusions:
- MVMp utilizes distinct pathways for cell cycle arrest during infection versus NS1 expression.
- p53 is essential for MVMp-induced S phase arrest, while both p53 and p21(cip1) are required for G2 arrest.
- NS1 induces G2 arrest via p21(cip1) inhibition of cyclin A-dependent kinase activity, suggesting a specific role for NS1 in viral replication.
More Related Videos
Related Concept Videos
Negative Regulator Molecules
DNA Damage can Stall the Cell Cycle
Inhibition of Cdk Activity
Abnormal Proliferation
DNA Damage Can Stall the Cell Cycle
Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...

