Wild-type p53 protein shows calcium-dependent binding to F-actin

Nuclear localization of p53 is required for p53 to detect and respond to DN A strand abnormalities and breaks following DNA damage. This leads to activ ation of the tumour suppressive functions of p53 resulting in either cell c ycle arrest and DNA repair; or apoptosis, Critical functional changes in DN A which require strand breaks, including gene rearrangement, may transientl y 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 in clude transient sequestering of p53 in the cytoplasm, Reversible nuclear-cy toplasmic shuttling is an intrinsic property of p53 (Middeler et al,, 1997) associated with cell cycle-related changes in p53's subcellular distributi on, Takahashi and Suzuki (1994) described p53 inactivation by shuttling to the cytoplasm and Katsumoto et al, (1995) found wildtype p53 to be closely associated,vith cytoplasmic actin filaments during DNA synthesis. Here we s how that, in the presence of free calcium ions, p53 binds directly to F-act in with a dissocation constant of about 10 mu M. Thus, part of the regulato ry machinery in normal cell cycling may involve p53-actin interactions regu lated by calcium fluxes and the dynamic turnover of F-actin.