Multiple pathways control cell growth and transformation: overlapping and independent activities of p53 and p21Cip1/WAF1/Sdi1.
Many tumour therapies act by inducing a cellular damage response pathway mediated by the tumour suppressor protein p53. Alternative outcomes of p53 induction include apoptosis or transient cell-cycle arrest, both thought to require the transcriptional activity of wild-type p53. Current research highlights the action of a p53-activated gene, p21Cip1/WAF1/Sdi1, which encodes a cyclin-kinase inhibitor important in mediating p53-dependent cell-cycle arrest, while programmed cell death in response to DNA damage requires transcriptionally active p53 but not activation of p21Cip1/WAF1/Sdi1. This review examines the roles of p53 and p21Cip1/WAF1/Sdi1 in controlling cell proliferation, in the light of a new study on expression of p53 and p21Cip1/WAF1/Sdi1 in squamous cell carcinoma of the larynx.
Cox
L S
LS
Department of Biochemistry, University of Oxford, U.K. lscox@bioch.ox.ac.uk
D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D014158:Transcription, Genetic
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins