p21: A Two-Faced Genome Guardian

Upon DNA damage or other stressors, the tumor suppressor p53 is activated, leading to transient expression of the cyclin-dependent kinase inhibitor (CKI) p21. This either triggers momentary G1 cell cycle arrest or leads to a chronic state of senescence or apoptosis, a form of genome guardianship. In...

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Bibliographic Details
Published in:Trends in molecular medicine 2017-04, Vol.23 (4), p.310-319
Main Authors: Georgakilas, Alexandros G, Martin, Olga A, Bonner, William M
Format: Article
Language:English
Subjects:
Animals
Apoptosis
cancer
Cyclin-Dependent Kinase Inhibitor p21 - genetics
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
DNA Damage
DNA Repair
error-prone repair
Gene Expression Regulation, Neoplastic
genomic instability
Humans
Neoplasms - genetics
Neoplasms - metabolism
p21 overexpression
p53 deficiency
Pathology
Tumor Suppressor Protein p53 - metabolism
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Summary:Upon DNA damage or other stressors, the tumor suppressor p53 is activated, leading to transient expression of the cyclin-dependent kinase inhibitor (CKI) p21. This either triggers momentary G1 cell cycle arrest or leads to a chronic state of senescence or apoptosis, a form of genome guardianship. In the clinic, the presence of p21 has been considered an indicator of wildtype p53 activity. However, recent evidence suggests that p21 also acts as an oncogenic factor in a p53-deficient environment. Here, we discuss the controversial aspects of the two-faced involvement of p21 in cancer and speculate on how this new information may increase our understanding of its role in cancer pathogenesis. Prevailing notions indicate that p21 might also act as antiapoptotic agent, which may have relevant implications for future therapeutic strategies.
ISSN:1471-4914
1471-499X
DOI:10.1016/j.molmed.2017.02.001