Altered distribution of the promyelocytic leukemia-associated protein is associated with cellular senescence.

نویسندگان

  • W Q Jiang
  • N Ringertz
چکیده

The disruption of the normal function and nuclear localization of the promyelocytic leukemia-associated protein (PML) may play a major role in the pathogenesis of acute promyelocytic leukemia. PML, which is concentrated in nuclear bodies (PML bodies), has been shown to have growth- and transformation-suppressive properties. In this study, we have examined the intranuclear distribution of PML in a conditionally immortalized human cell line (IDH4) in which both proliferation and immortalization are dependent on the presence of SV40-encoded large T-antigen (SV40T). Expression of SV40T is controlled by a dexamethasone (Dex)-inducible promotor. Suppression of SV40DT (Dex removal) in IDH4 cells causes G1 arrest and expression of the senescent phenotype. This is accompanied by a redistribution of PML in most cells from the usual pattern containing only spherical bodies to a pattern, containing large doughnut-like or fiber-like structures in addition to the spherical bodies. This change in pattern is reversed when phenotypically senescent IDH4 cells are stimulated to proliferate again by SV40T-induction. Moreover, we find that there is a similar change in the PML pattern between young and senescent or serum-starved young IMR90 human fibroblasts, from which IDH4 cells are derived. However, fewer serum-starved cells contain large PML bodies than senescent cells. Our observations suggest senescence, although it may be partly related to growth arrest. Using three-dimensional fluorescence digital imaging microscopy, we have found that the apparently doughnut-like PML structures have a cylindrical or egg-shaped form and that PML is concentrated to the outer shell of the structure.

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عنوان ژورنال:
  • Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research

دوره 8 5  شماره 

صفحات  -

تاریخ انتشار 1997