DISRUPTION OF ACTIN MICROFILAMENTS BY CYTOCHALASIN-D LEADS TO ACTIVATION OF P53

Activation of p53 plays a central role in the cell's response to vario us stress signals. We investigated whether p53 is activated upon disru ption of actin microfilaments, caused by cytochalasin D (CD). We show that treatment with CD leads to accumulation of p53 in the cells and a ctivation of p53-dependent transcription. Treatment with CD led to arr est of G1-to-S transition in cells retaining wild-type p53, while cell s with inactivated p53 showed partial rescue from it. CD also induces apoptosis in p53+/+, but not in p53-/- cells. The obtained data sugges t that disruption of the actin microfilaments activates p53-dependent pathways. (C) 1998 Federation of European Biochemical Societies.