The Ink4/Arf locus encodes two tumour-suppressor proteins, p16Ink4a and p19Arf, that govern the antiproliferative functions of the retinoblastoma and p53 proteins, respectively. Here we show that Arf binds to the product of the Mdm2 gene and sequesters it into the nucleolus, thereby preventing negative-feedback regulation of p53 by Mdm2 and leading to the activation of p53 in the nucleoplasm. Arf and Mdm2 co-localize in the nucleolus in response to activation of the oncoprotein Myc and as mouse fibroblasts undergo replicative senescence. These topological interactions of Arf and Mdm2 point towards a new mechanism for p53 activation.

Nucleolar Arf sequesters Mdm2 and activates p53.

Publisher Summary Autoantibodies to nuclear antigens (ANAs) have assumed an important place in the diagnostic armamentarium of the clinician because of distinct profiles of ANAs in different diseases. Profiles of ANAs have, therefore, been extremely useful in differential diagnosis, where the disease does not have classical or full-blown manifestations.. Immune complexes formed in the circulation or in situ mediate tissue injury by the activation of complement and other inflammatory mediators. Not only do these antibodies precipitate their respective antigens but also other proteins or nuclear RNAs that might be associated with them in special ways. The reasons for these special associations of protein antigens with specific sets of nuclear RNAs is unknown, but the possibility that there might be functional relationships in these complexed particles is not unreasonable. The key question that pervades the minds of many investigators in this field is the reason for the appearance of ANAs in certain individuals. It is highly improbable that the phenomenon is a random immune response to nuclear breakdown products, because the types of ANAs in different diseases are strikingly different. Some known environmental agents are drugs, such as hydralazine and procainamide, that together with lower levels of hepatic acetyltransferase enzyme predispose the host to the development of ANAs. Another agent may be the Epstein–Barr virus that is a ubiquitous environmental agent.

Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine.

How do the polyene macrolide antibiotics affect the cellular membrane properties

Retinoic acid regulates aberrant nuclear localization of PML-RARα in acute promyelocytic leukemia cells

DNA REPLICATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 TRANSCRIPTION AND PRE-mRNA PROCESSING .... . . ) ....... ,.... 279 Localization of Transcriptionally Active Nuclear Regions by [ HJ-Uridine Incorporation or In Situ Nick Translation . . . . . . . . . . . . . . . . 279 Pre-mRNA Splicing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280 An Arginine/Serine-Rich Domain Targets Proteins to Nuclear Speckles . . . . . . 284 Effect of RNA Polymerase II Transcription on the Localization of Splicing Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ,.... 285 Distribution of hnRNP Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 Localization of Splicing Factors in the Amphibian Germinal Vesicle . . . . . . . . 289 Localization of Splicing Factors in Yeast 290 Distribution of Poly(A)'t RNA . . . . . . ... . . . . ..... . ..... . . . . .... 291 Distribution of Specific Cellular Transcripts . . . . . . . . . . . . . . . . . . . . . . . 291 NUCLEOLAR ORGANIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293

Macromolecular domains within the cell nucleus.

Structure, function and assembly of the nucleolus.

In the present review on the organization of the mammalian cell nucleolus, we report and discuss data obtained during the past 10 years by means of cytochemical and immunocytochemical ultrastructural techniques. Particular emphasis is placed on the following topics: location of the nucleolus organizer regions in interphasic nucleolar components, structure of nucleolar chromatin in situ, and the structure-function relationship of the nucleolar components. The cytochemical and immunocytochemical results are compared and the concordant data are stressed for each topic.

Ultrastructural cytochemistry of the mammalian cell nucleolus.

High resolution autoradiographic studies of ehrlich tumour cell nucleoli. Nucleolar labelling after [3H]actinomycin D binding to DNA or after [3H]TdR or [3H]uridine incorporation in nucleic acids.

Modifications of cell shape induced in cultured newborn rat astroblasts by serum deprivation or dibutyryladenosine 3′–5′ monophosphate (dBcAMP) are described. Serum suppression modifies the adhesivity of the cells to the substrate, but this modification is not consistent with a true differentiation. The main ultrastructural feature of dBcAMP-treated astroblasts is the presence of an extensive system of 90 A microfilaments, while control cells are relatively devoid of these structures.

Comparative ultrastructural study of the effects of serum-free medium and dibutyryl-cyclic AMP on newborn rat astroblasts.

There is growing evidence that the cell nucleus like the cytoplasm is organized into different functional domains. The best-characterized intranuclear domain is the Nucleolus. This review presents and discusses recent progress in the understanding of nucleolar architecture and its relationship to nucleolar functions. Both the morphology and the composition of the various nucleolar components are analysed during the cell cycle in different eucaryotic organisms. Since controversy is still present in this field, the authors critically evaluate the data and propose a new model of structure-function relationships within the Nucleolus. This review is designed for researchers who need general information on the morphology and functions of the Nucleolus.

Guy Goessens

Papers

Structure, function and assembly of the nucleolus.

Ultrastructural cytochemistry of the mammalian cell nucleolus.

High resolution autoradiographic studies of ehrlich tumour cell nucleoli. Nucleolar labelling after [3H]actinomycin D binding to DNA or after [3H]TdR or [3H]uridine incorporation in nucleic acids.

Comparative ultrastructural study of the effects of serum-free medium and dibutyryl-cyclic AMP on newborn rat astroblasts.

The Nucleolus During the Cell Cycle