Phorbol esters induce transient changes in the accessibility of the carboxy-terminal domain of nuclear lamin A.
Treatment of human epithelial cells in culture with phorbol esters (TPA) gives rise to a transient and reversible loss of accessibility to antibodies of the nonhelical carboxy-terminal domain of nuclear lamin A that distinguishes it from lamin C. No change in the accessibility of epitopes present in the common domain of lamins A and C was observed. Loss of accessibility of lamin A was not due to proteolytic degradation nor to modification of the isoelectric point of lamin A and did not depend upon protein kinase C activation nor protein synthesis. Perturbation of desmosome organization by growth in low calcium blocked the effect of TPA on lamin A. Prolonged exposure to nocodazole, one of the effects of which is a perinuclear collapse of intermediate filaments, also blocked the effect of TPA on lamin A. These results suggest that the initial target of TPA may be at the level of cell-cell contacts and that the perturbation induced by TPA may be propagated via the structural link formed by intermediate filaments between the cell surface and the nucleus, giving rise to a change in conformation of the carboxy-terminal domain of lamin A or to an interaction of this domain with another nuclear component. These results form the basis for the hypothesis that the interphase nuclear lamina may play an active role in the process of mechanochemical signal transduction.
Collard
J F
JF
Institut du cancer de Montréal, Québec, Canada.
Raymond
Y
Y
D001666:Binding Sites, Antibody / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D003896:Desmosomes / Q000187:drug effects; D000939:Epitopes / Q000737:chemistry; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D034904:Lamin Type A; D034882:Lamins; D015739:Nocodazole; D009685:Nuclear Envelope / Q000187:drug effects*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects; D015398:Signal Transduction
D000939:Epitopes; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins; D010703:Phorbol Esters; C440308:lamin C; D015739:Nocodazole; D002118:Calcium