Abstract
Nuclear localization of p53 is required for p53 to detect and respond to DNA strand abnormalities and breaks following DNA damage. This leads to activation of the tumour suppressive functions of p53 resulting in either cell cycle arrest and DNA repair; or apoptosis. Critical functional changes in DNA which require strand breaks, including gene rearrangement, may transiently mimic DNA damage: here it is important not to trigger a p53 response. The fine control of p53 in these different circumstances is unknown but may include transient sequestering of p53 in the cytoplasm. Reversible nuclear-cytoplasmic shuttling is an intrinsic property of p53 (Middeler et al., 1997) associated with cell cycle-related changes in p53's subcellular distribution. Takahashi and Suzuki (1994) described p53 inactivation by shuttling to the cytoplasm and Katsumoto et al. (1995) found wild-type p53 to be closely associated with cytoplasmic actin filaments during DNA synthesis. Here we show that, in the presence of free calcium ions, p53 binds directly to F-actin with a dissocation constant of about 10 μM. Thus, part of the regulatory machinery in normal cell cycling may involve p53-actin interactions regulated by calcium fluxes and the dynamic turnover of F-actin.
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This work was funded by Yorkshire Cancer Research and the UK Medical Research Council.
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Metcalfe, S., Weeds, A., Okorokov, A. et al. Wild-type p53 protein shows calcium-dependent binding to F-actin. Oncogene 18, 2351–2355 (1999). https://doi.org/10.1038/sj.onc.1202559
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DOI: https://doi.org/10.1038/sj.onc.1202559
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