Nucleolus

About: Nucleolus is a research topic. Over the lifetime, 5873 publications have been published within this topic receiving 232435 citations. The topic is also known as: GO:0005730 & cell nucleolus.

PML regulates p53 stability by sequestering Mdm2 to the nucleolus.

Abstract: The promyelocytic leukaemia (PML) tumour-suppressor protein potentiates p53 function by regulating post-translational modifications, such as CBP-dependent acetylation and Chk2-dependent phosphorylation, in the PML-Nuclear Body (NB). PML was recently shown to interact with the p53 ubiquitin-ligase Mdm2 (refs 4-6); however, the mechanism by which PML regulates Mdm2 remains unclear. Here, we show that PML enhances p53 stability by sequestering Mdm2 to the nucleolus. We found that after DNA damage, PML and Mdm2 accumulate in the nucleolus in an Arf-independent manner. In addition, we found that the nucleolar localization of PML is dependent on ATR activation and phosphorylation of PML by ATR. Notably, in Pml(-/-) cells, sequestration of Mdm2 to the nucleolus was impaired, as well as p53 stabilization and the induction of apoptosis. Furthermore, we demonstrate that PML physically associates with the nucleolar protein L11, and that L11 knockdown impairs the ability of PML to localize to nucleoli after DNA damage. These findings demonstrate an unexpected role of PML in the nucleolar network for tumour suppression.

Differential synthesis of the genes for ribosomal RNA during amphibian oögenesis.

Abstract: Molecular hybridization experiments have shown that the genes for ribosomal RNA are located in or near the nucleolus organizer in Drosophila melanogasterl' 2 and in the toad Xenopus laevis.3' 4 Under normal circumstances the number of organizers per genome will be characteristic of the organism, and DNA from various tissues should contain the same proportion of ribosomal genes. This conclusion has been confirmed for several tissues of the chicken.2 However, cytological evidence has long suggested that the nucleolus organizer undergoes a differential replication in oocytes of certain animals. Data supporting this view will be summarized later in this article. If such a differential replication occurs, oocyte DNA should be enriched with respect to the ribosomal genes. The cytological picture is particularly striking in ovaries of the toads Bufo and Xenopus, in which the differential synthesis occurs during pachytene. In recently metamorphosed toads the ovary contains a sufficiently high proportion of pachytene o6cytes to permit detection of the differential synthesis by biochemical means.5 This communication describes the ovarian DNA of Xenopus and demonstrates that it contains an excess of sequences coding for rRNA. Recently Brown and co-workers6' 7 have studied the DNA from older oocytes of Xenopus and have reached similar conclusions.

U3, U8 and U13 comprise a new class of mammalian snRNPs localized in the cell nucleolus

Abstract: Using anti-(U3)RNP autoantibodies, we have isolated and characterized two additional small nucleolar RNAs from HeLa cells, which are less abundant than U3 RNA. Both RNAs possess a trimethylguanosine cap as judged by precipitation with anti-TMG antibody, but are not precipitated by either anti-Sm or anti-La antibodies. In addition, both RNAs are not precipitable by anti-Th serum, which recognizes another nucleolar RNP autoantigen. Sequence analysis revealed that one of these RNAs, 136 nucleotides long, is the human U8 homolog; while the other, 105 nucleotides long, represents a novel species which we designate U13. Both RNAs share with U3 two conserved sequences (boxes C and D). The role of one or both of these boxes in binding the common 34 kd antigenic protein, otherwise known as fibrillarin, is discussed. Fractionation of HeLa cells revealed that U8 and U13, like U3, reside in the nucleolus. In glycerol gradients both RNAs cosediment with larger structures possibly representing ribosomal precursors. We propose that U3, U8 and U13 comprise a new subset of mammalian snRNPs whose roles in ribosome biogenesis are discussed.

Nucleolar Localization of Parathyroid Hormone-Related Peptide Enhances Survival of Chondrocytes under Conditions That Promote Apoptotic Cell Death

Abstract: Parathyroid hormone-related peptide (PTHrP) is a mediator of cellular growth and differentiation as well as a cause of malignancy-induced hypercalcemia. Most of the actions of PTHrP have been attributed to its interaction with a specific cell surface receptor that binds the N-terminal domain of the protein. Here we present evidence that PTHrP promotes some of its cellular effects by translocating to the nucleolus. Localization of transiently expressed PTHrP to the nucleolus was dependent on the presence of a highly basic region at the carboxyl terminus of the molecule that bears homology to nucleolar targeting sequences identified within human retroviral (human immunodeficiency virus type 1 and human T-cell leukemia virus type 1) regulatory proteins. Endogenous PTHrP also localized to the nucleolus in osseous cells in vitro and in vivo. Moreover, expression of PTHrP in chondrocytic cells (CFK2) delayed apoptosis induced by serum deprivation, and this effect depended on the presence of an intact nucleolar targeting signal. The present findings demonstrate a unique intracellular mode of PTHrP action and a novel mechanism by which this peptide growth factor may modulate programmed cell death.