UV induces nucleolar translocation of ING1 through two distinct nucleolar targeting sequences

Scott, Michelle S.; Boisvert, François‐Michel; Vieyra, Diego; Johnston, Randal N.; Bazett-Jones, David P.; Riabowol, Karl

doi:10.1093/nar/29.10.2052

Cited by 103 publications

(109 citation statements)

References 29 publications

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“…The characteristic nucleolar localization of p14ARF or p19ARF was not affected by the levels of p33ING1 in any case (compare middle and bottom panels in Figure 2a, c and e). It is worth mentioning that a similar accumulation of p33ING1 in nucleoli has been described to occur in human diploid fibroblasts upon exposure to high doses of UV radiation (Scott et al, 2001a). In that study, mutant versions of the p33ING1 protein that did not relocalize in the nucleolus showed a reduced ability to induce apoptosis.…”

supporting

confidence: 66%

“…In this regard, recent reports show that ARF plays an important role in ribosomal biogenesis, in the nucleolus (Itahana et al, 2003;Sugimoto et al, 2003;Bertwistle et al, 2004). As p33ING1 can also accumulate in the nucleolus (Figure 2; see also Scott et al, 2001a), a possible functional connection at this level is possible. More importantly, there is ample evidence, both in mammals and yeast, showing that ING proteins can form complexes with histone deacetylases and histone acetyltransferases.…”

mentioning

confidence: 77%

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A functional link between the tumour suppressors ARF and p33ING1

et al. 2006

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The ARF tumour suppressor protein plays a critical role in the activation of p53 in response to oncogenic stress. ARF can activate p53 through nucleolar sequestration of Mdm2. However, several lines of evidence indicate that this is not the only way of action of ARF, and alternative mechanisms must exist. p33ING1 is a putative tumour suppresor, which induces cell-cycle arrest and apoptosis in a p53-dependent manner. Here, we describe that ARF and p33ING1 can interact in vivo. We also show that the subcellular localization of ING1 can be modulated by ARF protein levels, causing a displacement from nuclear to nucleolar localization. Finally, the ability of p33ING1 to cause cell-cycle arrest and induction of p21CIP1, or Mdm2, is impaired in ARF-deficient primary mouse fibroblasts. Based on these observations, we propose that the interaction with p33ING1 represents a novel mechanism for the tumour suppression function of ARF.

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supporting

confidence: 66%

mentioning

confidence: 77%

A functional link between the tumour suppressors ARF and p33ING1

et al. 2006

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“…By looking for sequential similarities between the hLa-NoLS described here and other published sequences mediating nucleolar localization of different human proteins (45)(46)(47)(48)(49)(50)(51)(75)(76)(77)(78), we aligned those sequences with the hLa-NoLS (Fig. 4C).…”

Section: Discussionmentioning

confidence: 99%

“…Because elements for nucleolar localization have been described for other proteins (45)(46)(47)(48)(49)(50)(51)(52), it is conceivable to assume that hLa bears such a signal to ensure its interaction with pre-tRNAs, for example, in the nucleolus besides the binding of pre-U3 snoRNA or U6 snRNA in the nucleoplasm. In this report we identified a yet unknown nucleolar localization signal (NoLS) in the C-terminal region of hLa, and we show that it functions in a heterologous context.…”

mentioning

confidence: 99%

Nuclear Trafficking of La Protein Depends on a Newly Identified Nucleolar Localization Signal and the Ability to Bind RNA

Horke

Reumann

Schweizer

et al. 2004

Journal of Biological Chemistry

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Here we provide evidence for an interaction-dependent subnuclear trafficking of the human La (hLa) protein, known as transient interaction partner of a variety of RNAs. Among these, precursor transcripts of certain RNAs are located in the nucleoplasm or nucleolus. Here we examined which functional domains of hLa are involved in its nuclear trafficking. By using green fluorescent-hLa fusion proteins, we discovered a nucleolar localization signal and demonstrated its functionality in a heterologous context. In addition, we revealed that the RRM2 motif of hLa is essential both for its RNA binding competence in vitro and in vivo and its exit from the nucleolus. Our data imply that hLa traffics between different subnuclear compartments, which depend decisively on a functional nucleolar localization signal as well as on RNA binding. Directed trafficking of hLa is fully consistent with its function in the maturation of precursor RNAs located in different subnuclear compartments.The human La protein (hLa) 1 is a 47-kDa phosphoprotein predominantly localized in the nucleus. It was first discovered as an autoantigen recognized by antibodies present in the sera of patients suffering from systemic lupus erythematosus and Sjogren's syndrome (1, 2). The La protein is a member of a large group of RNA-binding proteins containing RNA recognition motifs (RRMs) (3-7) and interacts with a variety of small RNAs (for reviews see Refs. 8 -10). The La protein is implicated in several aspects of the RNA metabolism, including processing of precursors of tRNAs, U3 snoRNA, U1 RNA, U6 snRNA (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), and stabilization of viral (21-23) as well as cellular RNAs (24). In the cytoplasm, La has been implicated in the translational control of viral (25-27) and cellular RNAs (28 -30).The human La protein contains a nuclear localization sequence at the very C-terminal end, and the staining for endogenous La as well as the distribution of GFP-tagged La reveal a predominantly diffuse nuclear staining, although this may appear different under certain conditions or treatments (31-33). Subcellular distribution of human and yeast La was assumed to be independent of phosphorylation (34, 35); however, recent studies (36, 37) revealed that phosphorylation at Ser-366 may well influence subcellular localization of La. A regulated, nonhomogeneous nuclear distribution of La may also be predicted from the distinct nuclear distribution of its various RNA interaction partners. For instance, pre-tRNAs are most likely synthesized in the nucleoplasm (38) but are processed, at least in part, in the nucleolus (39, 40), whereas in yeast the La-associated precursor of U3 snoRNA is probably processed in the nucleolar body and nucleolus (20). Nevertheless, interactions with precursor RNAs in different nuclear compartments implicate a highly dynamic and regulated nuclear distribution of La. Although a nucleolar localization of La has been reported (for review see Ref. 9), the hLa protein was not identified among the recently resolved protein ...

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“…Overexpression of DEDD, for instance, can make this protein to translocate to the nucleus (Schickling et al, 2001) as associated with caspase 8/10 (Alcivar et al, 2003) and to co-localize with UBF in the nucleolus; since in vitro DEDD is capable of inhibiting transcription, this suggests that DEDD might be involved in shutting-off the cell biosynthetic activities. Several other nuclear and nucleolar proteins have been reported to move to ectopic locations during apoptosis; among them, B23 was found to translocate from the nucleolus to the nucleoplasm in daunomycin-induced apoptosis (Chan and Chan, 1999), while the candidate tumor suppressor protein, ING1 moves the nucleolus and this translocation may facilitate apoptosis in UV-treated cells (Scott et al, 2001). Martelli et al (2000) reported that some nucleolar antigens (namely, PARP-1 and UBF) are cleaved during apoptosis, whereas others (fibrillarin, B23 and C23) are not; cleavage of topoisomerase I and B23 has been shown to occur in cis-DDP-induced apoptosis (Horky et al, 2001).…”

Section: Nucleoplasmic and Nucleolar Rnps In Apoptosismentioning

confidence: 99%

Rearrangement of nuclear ribonucleoprotein (RNP)‐containing structures during apoptosis and transcriptional arrest

Biggiogera

Bottone

Scovassi

et al. 2004

Biology of the Cell

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The aim of this paper is to review the data in the literature concerning ribonucleoprotein components during apoptosis, where a major rearrangement of RNPs takes place. In parallel with chromatin changes, the nucleoplasmic constituents (perichromatin fibrils; perichromatin granules; interchromatin granules and nuclear bodies) as well as the nucleoli aggregate into heterogeneous clusters called HERDS, in the interchromatin space. Later, these RNP-containing structures are extruded from the nucleus and leave the cell within cytoplasmic blebs. We propose also a role for HERDS as markers of irreversible transcriptional arrest. © 2004 Elsevier SAS. All rights reserved.Keywords: Electron microscopy; HERDS; Immunocytochemistry; Nuclear ribonucleoproteins; Transcription The cell nucleus during apoptosis: an introductionThe basic functions of the nucleus such as replication, transcription, DNA repair and their timing, as well as the correct sorting of information need an architectural support; this support, however, needs not to be a stable structural one only, but preferably derived from the dynamic interaction of many different components to be -at the same time-flexible and stable enough for these processes to proceed (Marshall, 2002;Stein et al., 2003).The nucleus is compartmentalized, both structurally and functionally and, in fact, may be considered as composed of at least two largely interacting parts: chromatin and the ribonucleoprotein (RNP)-containing structures. Already during the sixties of the last century, Bernhard and co-workers (Bernhard, 1969;Monneron and Bernhard, 1969; Bernhard, 1971,1973) showed that, thanks to a rather simple ultrastructural technique based on treatment with EDTA, condensed chromatin may be quite efficiently bleached whereas the interchromatin space becomes more contrasted. Under these conditions, it was possible -for the very first time-to detect and describe in detail some RNP-based structures. Those pioneering papers have then been followed by a plethora of articles aimed at elucidating the organization, chemical composition and functional significance of nuclear RNPs (for a recent review, see Fakan, 2004, and Table 1). One specific region (or domain), perichromatin compartment, is of particular interest since it is the place where most of the functions related to transcription, splicing and gene silencing are located (Cmarko et al., 2003).It is now widely accepted that, in eukaryotic cells, nuclear RNPs are part of the transcription and splicing machinery, and are always organized as morphologically recognizable structures (as schematically reported in Fig. 1a); at the electron microscope, these structures have been described as perichromatin fibrils (PF), perichromatin granules (PG), and interchromatin granules (IG) (Fakan, 1994;Spector, 1996), and nucleolus (Raška et al., 2004, in this issue). These structures are characterized by the presence of some marker proteins, such as hnRNP core proteins in PF (Martin and Okamura, 1981;Fakan et al., 1984), SC-35, Sm and PANA ...

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UV induces nucleolar translocation of ING1 through two distinct nucleolar targeting sequences

Cited by 103 publications

References 29 publications

A functional link between the tumour suppressors ARF and p33ING1

A functional link between the tumour suppressors ARF and p33ING1

Nuclear Trafficking of La Protein Depends on a Newly Identified Nucleolar Localization Signal and the Ability to Bind RNA

Rearrangement of nuclear ribonucleoprotein (RNP)‐containing structures during apoptosis and transcriptional arrest

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