The interaction of p53 with the nuclear matrix is mediated by F-actin and modulated by DNA damage.
The tumour suppressor protein p53 is localized in the cell nucleus where it serves to initiate cellular responses to a variety of stresses, particularly DNA damage and has the capacity to transactivate stress response genes. An emerging body of evidence indicates that its action is also exerted through direct protein-protein interactions. An approach to understanding p53 function has been to analyse its positioning in relation to nuclear structures and we have shown that p53 can associate with the nuclear matrix. A potential nuclear matrix component for this association is actin. Here we show that p53 interacts with nuclear F-actin and we map the domains involved in this interaction. Using fluorescence resonance energy transfer, we demonstrate that the partition of p53 between F-actin bound and unbound forms is not constant, but is modulated by the presence of DNA damage, which increases binding. Our results indicate that the dynamic interaction of p53 with the nuclear matrix has to be considered for a full understanding of the mechanisms of the p53-mediated cellular response to DNA damage.
Okorokov
Andrei L
AL
YCR P53 Research Group, Department of Biology, University of York, York, YO10 5DD, UK.
Rubbi
Carlos P
CP
Metcalfe
Su
S
Milner
Jo
J
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D004249:DNA Damage / Q000528:radiation effects; D004735:Energy Transfer; D018260:Gelsolin / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009154:Mutation; D015530:Nuclear Matrix / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D000199:Actins; D018260:Gelsolin; D016159:Tumor Suppressor Protein p53