Archives of Toxicology

, Volume 89, Issue 2, pp 155–178 | Cite as

Biology of the cell cycle inhibitor p21CDKN1A: molecular mechanisms and relevance in chemical toxicology

  • Ilaria Dutto
  • Micol Tillhon
  • Ornella Cazzalini
  • Lucia A. Stivala
  • Ennio ProsperiEmail author
Review Article


The cell cycle inhibitor p21CDKN1A is a protein playing multiple roles not only in the DNA damage response, but also in many cellular processes during unperturbed cell growth. The main, well-known function of p21 is to arrest cell cycle progression by inhibiting the activity of cyclin-dependent kinases. In addition, p21 is involved in the regulation of transcription, apoptosis, DNA repair, as well as cell motility. However, p21 appears to a have a dual-face behavior because, in addition to its tumor suppressor functions, it may act as an oncogene, depending on the cell type and on the cellular localization. As a biomarker of the cell response to different toxic stimuli, p21 expression and functions have been analyzed in an impressive number of studies investigating the activity of several types of chemicals, in order to determine their possible harmful effects on human cells. Here, we review these studies in order to highlight the different roles p21 may play in the cell response to chemical exposure and to better evaluate the information provided by this biomarker.


p21CDKN1A/WAF1/CIP1 Cell cycle inhibition DNA damage response DNA repair Genotoxic compounds Chemical toxicity 



Aflatoxin B1


Apoptosis signal-regulating kinase-1


Base excision repair


CDK-activating kinase


CREB-binding protein


Cyclin-dependent kinase


Cytolethal distending toxin


Chronic obstructive pulmonary disease


Cigarette smoke


Endocrine-disrupting chemical


Estrogen receptor-α




Mismatch repair


Nucleotide excision repair




Nuclear localization signal




Neural stem cell




Ochratoxin A


Proliferating cell nuclear antigen


RNA-binding proteins


Reactive oxygen species


Translesion DNA synthesis



Owing to space limitations, it has been not possible to cite several works dealing with p21 and aspects related to chemical toxicity; we apologize to these Authors. Work in the Author’s lab has been supported by Grants AIRC (5126 and 11747 to EP), and previously by a MIUR Grant to LS. ID is a Ph.D. student of IUSS (Pavia).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ilaria Dutto
    • 1
  • Micol Tillhon
    • 1
  • Ornella Cazzalini
    • 2
  • Lucia A. Stivala
    • 2
  • Ennio Prosperi
    • 1
    Email author
  1. 1.Genome Stability Group, Institute of Molecular GeneticsNational Research Council (CNR)PaviaItaly
  2. 2.General Pathology and Immunology Unit, Department of Molecular MedicineUniversity of PaviaPaviaItaly

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