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Mutant p53 rescues human diploid cells from senescence without inhibiting the induction of SDI1/WAF1

Bond, J.A., Blaydes, J. P., Rowson, J., Haughton, M. F., Smith, J. R., Wynford-Thomas, D. and Wyllie, F. S. (1995) Mutant p53 rescues human diploid cells from senescence without inhibiting the induction of SDI1/WAF1 Cancer Research, 55, (11), pp. 2404-9.

Record type: Article


Although the cyclin-dependent kinase inhibitor p21SDI1 (WAF1/CIP1) has been proposed as the mediator of p53-induced cell cycle arrest following DNA damage, several stimuli now appear to induce SDI1 independent of p53 function. We have examined the behavior of p53 and SDI1 in an isogeneic model by manipulating p53 status in normal diploid human fibroblasts using an amphotropic retroviral vector. Following DNA strand break damage induced by bleomycin, both SDI1 induction and G1-S cell cycle arrest are p53 dependent, consistent with SDI1 being the key mediator. In contrast, in cellular senescence (and following UV irradiation), induction of SDI1 occurs independent of p53 function yet growth arrest is still p53 dependent. We conclude (a) that redundant pathways exist for induction of SDI1, but that (b) SDI1, while perhaps necessary, is not sufficient for inhibition of cell cycle progression, requiring the cooperation of an additional factor (possibly another cyclin-dependent kinase inhibitor) whose expression, at least in the case of senescence, is strictly p53 dependent.

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Published date: 1 June 1995


Local EPrints ID: 150587
ISSN: 0008-5472
PURE UUID: b32bf8fa-7535-4745-9f1d-ebd5489ef3f0

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Date deposited: 20 Jul 2010 15:10
Last modified: 18 Jul 2017 12:57

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Author: J.A. Bond
Author: J. P. Blaydes
Author: J. Rowson
Author: M. F. Haughton
Author: J. R. Smith
Author: D. Wynford-Thomas
Author: F. S. Wyllie

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