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.

Bioinformatic analysis of the nucleolus.

Abstract: The nucleolus is a plurifunctional, nuclear organelle, which is responsible for ribosome biogenesis and many other functions in eukaryotes, including RNA processing, viral replication and tumour suppression. Our knowledge of the human nucleolar proteome has been expanded dramatically by the two recent MS studies on isolated nucleoli from HeLa cells [Andersen, Lyon, Fox, Leung, Lam, Steen, Mann and Lamond (2002) Curr. Biol. 12, 1-11; Scherl, Coute, Deon, Calle, Kindbeiter, Sanchez, Greco, Hochstrasser and Diaz (2002) Mol. Biol. Cell 13, 4100-4109]. Nearly 400 proteins were identified within the nucleolar proteome so far in humans. Approx. 12% of the identified proteins were previously shown to be nucleolar in human cells and, as expected, nearly all of the known housekeeping proteins required for ribosome biogenesis were identified in these analyses. Surprisingly, approx. 30% represented either novel or uncharacterized proteins. This review focuses on how to apply the derived knowledge of this newly recognized nucleolar proteome, such as their amino acid/peptide composition and their homologies across species, to explore the function and dynamics of the nucleolus, and suggests ways to identify, in silico, possible functions of the novel/uncharacterized proteins and potential interaction networks within the human nucleolus, or between the nucleolus and other nuclear organelles, by drawing resources from the public domain.

MDM2-ARF complex regulates p53 sumoylation

Abstract: The p53 tumor suppressor is regulated by MDM2-mediated ubiquitination and degradation. Ubiquitination of p53 is regulated by ARF, which binds to MDM2 and inhibits its E3 ligase function. P53 is also subjected to modification by conjugation of SUMO-1. We found that a p53 mutant deficient for MDM2 binding (p53(14Q19S)) is poorly sumoylated in vivo compared to wild-type p53. Overexpression of MDM2 increases the level of p53 sumoylation, which is further stimulated by expression of ARF. Stimulation of p53 sumoylation requires a highly conserved region (102-116) encoded by exon 2 of ARF and correlates with the ability of ARF to target p53 to the nucleolus. An MDM2 deletion mutant (MDM2(Delta222-437)) with activated cryptic nucleolar localization signal also targets p53 to the nucleolus and efficiently promotes p53 sumoylation in the absence of ARF. Direct targeting of p53 to the nucleolus enhances its sumoylation in an MDM2- and ARF-dependent fashion. These results show that p53 sumoylation is regulated by MDM2- and ARF-mediated nucleolar targeting.

Nucleolar Sequestration of RelA (p65) Regulates NF-κB-Driven Transcription and Apoptosis

Abstract: The molecular mechanisms that regulate nuclear NF-κB to determine whether the stimulation of this pathway has a pro- or antiapoptotic effect on cells have yet to be fully defined. Nuclear compartmentalization is increasingly recognized as an important mechanism for regulating the activity of transcription-related proteins and modulating cell growth and death. We have investigated whether such compartmentalization serves as a mechanism for regulating NF-κB transcriptional activity. We demonstrate that the RelA component of NF-κB is sequestered in the nucleolus in response to the proapoptotic NF-κB stimuli aspirin, serum withdrawal, and UV-C radiation. In contrast, RelA is excluded from the nucleolus in response to the cytokines tumor necrosis factor and TRAIL. We identify an N-terminal motif of RelA that is essential for the nucleolar localization of the protein and show that deleting this motif inhibits the translocation of RelA from the nucleoplasm to the nucleolus. We demonstrate that the nucleolar accumulation of RelA is paralleled by a decrease in basal levels of NF-κB transcriptional activity and by apoptosis. Furthermore, we show that the retention of RelA in the nucleoplasm inhibits this decrease in NF-κB-driven transcription and blocks apoptosis induced by aspirin and UV-C radiation. This work identifies a novel cellular mechanism for regulating NF-κB-driven transcription and apoptosis, involving the nucleolar sequestration of a key NF-κB subunit. These data contribute to the understanding of the complexities of NF-κB function and have considerable relevance to cancer prevention and therapy.

Initiation of Nucleolar Assembly Is Independent of RNA Polymerase I Transcription

Abstract: This report examines the distribution of an RNA polymerase I transcription factor (upstream binding factor; UBF), pre-rRNA processing factors (nucleolin and fibrillarin), and pre-rRNAs throughout mitosis and postmitotic nucleologenesis in HeLa cells. The results demonstrate that nucleolin, fibrillarin, and pre-rRNAs synthesized at G2/M phase of the previous cell cycle are directly recruited to UBF-associated nucleolar organizer regions (NORs) early in telophase before chromosome decondensation. Unlike the fusion of prenucleolar bodies to the nucleoli, this early recruitment of processing factors and pre-rRNAs is independent of RNA polymerase I transcription. In the absence of polymerase I transcription, the initial localization of nucleolin, fibrillarin, and pre-rRNAs to UBF-associated NORs generates segregated mininucleoli that are similar to the larger ones observed in interphase cells grown under the same conditions. Pre-rRNAs are juxtaposed to UBF-nucleolin-fibrillarin caps that may represent the segregated nucleoli observed by electron microscopy. These findings lead to a revised model of nucleologenesis. We propose that nucleolar formation at the end of mitosis results from direct recruitment of processing factors and pre-rRNAs to UBF-associated NORs before or at the onset of rDNA transcription. This is followed by fusion of prepackaged prenucleolar bodies into the nucleolus. Pre-ribosomal ribonucleoproteins synthesized in the previous cell cycle may contribute to postmitotic nucleologenesis.