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 various stress signals. We investigated whether p53 is activated upon disruption of actin microfilaments, caused by cytochalasin D (CD). We show that treatment with CD leads to accumulation of p53 in the cells and activation of p53-dependent transcription. Treatment with CD led to arrest of G1-to-S transition in cells retaining wild-type p53, while cells with inactivated p53 showed partial rescue from it. CD also induces apoptosis in p53+/+, but not in p53-/- cells. The obtained data suggest that disruption of the actin microfilaments activates p53-dependent pathways.
Belozersky Institute of Physical and Chemical Biology, Moscow State University, Russia.
S N
SN
Rubtsova
R V
RV
Kondratov
P B
PB
Kopnin
P M
PM
Chumakov
B P
BP
Kopnin
J M
JM
Vasiliev
D008841:Actin Cytoskeleton / Q000187:drug effects*; D000199:Actins / Q000187:drug effects; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology*; D005347:Fibroblasts; D051379:Mice; D051381:Rats; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000199:Actins; D016159:Tumor Suppressor Protein p53; D015638:Cytochalasin D