PML protein association with specific nucleolar structures differs in normal, tumor and senescent human cells.
Promyelocytic leukemia protein (PML), a tumor suppressor, forms in most human cell types discrete multiprotein complexes termed PML nuclear bodies. Here, we have used indirect immunofluorescence and confocal microscopy to describe various forms of a novel nuclear PML compartment associated with nucleoli that is found under growth-permitting conditions in human mesenchymal stem cells (hMSC) and skin fibroblasts but not in several immortal cell lines with defects in the p53 and pRb pathways. In addition, we found that shut-off of rRNA synthesis induced by actinomycin D causes PML translocation to the surface of segregated nucleoli. This translocation is dynamic and reversible, following changes in nucleolar activity. Intriguingly, treatment causing premature senescence restores PML binding to nucleoli-derived structures and to the surface of segregated nucleoli in HeLa cells. These findings indicate that PML may be involved in nucleolar functions of normal non-transformed or senescent cells. The absence of nucleolar PML compartment in rapidly growing tumor-derived cells suggests that PML association with the nucleolus might be important for cell-cycle regulation.
Janderová-Rossmeislová
Lenka
L
Department of Cell Ultrastructure and Molecular Biology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.
Nováková
Zora
Z
Vlasáková
Jana
J
Philimonenko
Vlada
V
Hozák
Pavel
P
Hodný
Zdenek
Z
D002460:Cell Line; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000737:chemistry / Q000648:ultrastructure*; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D009369:Neoplasms / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D021381:Protein Transport; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism*
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human