Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control

Abstract

p21CIP1/WAF1 is a CDK inhibitor regulated by the tumor suppressor p53 and is hypothesized to mediate G1 arrest. p53 has been suggested to derive anti-oncogenic properties from this relationship. To test these notions, we created mice lacking p21CIP1/WAF1. They develop normally and (unlike p53-/- mice) have not developed spontaneous malignancies during 7 months of observation. Nonetheless, p21-/- embryonic fibroblasts are significantly deficient in their ability to arrest in G1 in response to DNA damage and nucleotide pool perturbation. p21-/- cells also exhibit a significant growth alteration in vitro, achieving a saturation density as high as that observed in p53-/- cells. In contrast, other aspects of p53 function, such as thymocytic apoptosis and the mitotic spindle checkpoint, appear normal. These results establish the role of p21CIP1/WAF1 in the G1 checkpoint, but suggest that the anti-apoptotic and the anti-oncogenic effects of p53 are more complex.

Keywords

BiologyG2-M DNA damage checkpointDNA damageCell cycle checkpointMitosisCell biologyApoptosisCyclin-dependent kinaseSuppressorCancer researchCell cycleGeneticsDNACancer

MeSH Terms

AnimalsApoptosisBase SequenceCell DifferentiationCell DivisionCell LineCyclin-Dependent Kinase Inhibitor p21CyclinsDNADNA DamageG1 PhaseGenesp53MiceMolecular Sequence DataNeoplasmsExperimentalSpindle ApparatusTumor Suppressor Protein p53

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Publication Info

Year: 1995
Type: article
Volume: 82
Issue: 4
Pages: 675-684
Citations: 2106
Access: Closed

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APA Style

                            
                                
                                    Chu‐Xia Deng, 
                                
                                    Pumin Zhang, 
                                
                                    J. Wade Harper
                                
                                et al.
                            
                            (1995). 
                            Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. 
                            Cell
                            , 82
                            (4)
                            , 675-684.
                            https://doi.org/10.1016/0092-8674(95)90039-x
                        

Identifiers

DOI: 10.1016/0092-8674(95)90039-x
PMID: 7664346

Data Quality

Data completeness: 90%