PML protein association with specific nucleolar structures differs in normal, tumor and senescent human cells.

Abstract

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.

• Authors: Lenka Janderová-Rossmeislová, Zora Nováková, Jana Vlasáková, Vlada Philimonenko, Pavel Hozák, Zdenek Hodný
• Journal: Journal of structural biology (J Struct Biol) Vol. 159 Issue 1 Pg. 56-70 (Jul 2007) ISSN: 1047-8477 [Print] United States
• PMID: 17428679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins
• Nuclear Proteins
• Promyelocytic Leukemia Protein
• Transcription Factors
• Tumor Suppressor Proteins
• PML protein, human

Topics

• Cell Line
• Cell Line, Tumor
• Cell Nucleolus (chemistry, ultrastructure)
• Cellular Senescence
• Fibroblasts (cytology)
• HeLa Cells
• Humans
• Mesenchymal Stem Cells (cytology)
• Microscopy, Fluorescence
• Neoplasm Proteins (analysis, metabolism)
• Neoplasms (pathology)
• Nuclear Proteins (analysis, metabolism)
• Promyelocytic Leukemia Protein
• Protein Transport
• Transcription Factors (analysis, metabolism)
• Tumor Suppressor Proteins (analysis, metabolism)