title: p21WAF1 and tumourigenesis:  20 years after.
abstract: OBJECTIVE
  This review provides an overview of the structure, regulation and physiological functions of p21, the product of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene, with a focus on its dual role in promoting and repressing biological processes that are hallmarks of tumourigenesis.
  
  
  RESULTS
  Recent work has provided a better understanding of the molecular mechanisms of how oncogenic signalling pathways influence p21 expression. In response to cellular stimuli, p21 expression is tightly regulated at transcriptional and post-translational levels through mechanisms involving RNA stabilization, phosphorylation and ubiquitination. As a result, growing evidence reveals that several important tumour suppressor and oncogenic signalling pathways alter p21 expression to elicit their effects on cell cycle progression and survival. Thus, p21 expression can both promote and inhibit tumourigenic processes, depending on the cellular context.
  
  
  CONCLUSIONS
  Since its discovery, it has become increasingly clear that p21 can function as both a classical tumour suppressor and an oncogene. In order to effectively utilize p21 as a therapeutic target, it will be necessary to design therapeutic strategies that preferentially block the ability of p21 to promote senescence, stem cell renewal and cyclin/CDK activation, while leaving its tumour suppressive functions intact.
authors.affiliation: Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Department of Medicine (Hematology/Oncology), Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: Noel A
authors.initials: NA
authors.lastname: Warfel
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D016158:Genes, p53; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21