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PMID:10504293

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Citation

Everett, RD, Earnshaw, WC, Pluta, AF, Sternsdorf, T, Ainsztein, AM, Carmena, M, Ruchaud, S, Hsu, WL and Orr, A (1999) A dynamic connection between centromeres and ND10 proteins. J. Cell. Sci. 112 ( Pt 20):3443-54

Abstract

ND10, otherwise known as nuclear dots, PML nuclear bodies or PODs, are punctate foci in interphase nuclei that contain several cellular proteins. The functions of ND10 have not been well defined, but they are sensitive to external stimuli such as stress and virus infection, and they are disrupted in malignant promyelocytic leukaemia cells. Herpes simplex virus type 1 regulatory protein Vmw110 induces the proteasome-dependent degradation of ND10 component proteins PML and Sp100, particularly the species of these proteins which are covalently conjugated to the ubiquitin-like protein SUMO-1. We have recently reported that Vmw110 also induces the degradation of centromere protein CENP-C with consequent disruption of centromere structure. These observations led us to examine whether there were hitherto undetected connections between ND10 and centromeres. In this paper we report that hDaxx and HP1 (which have been shown to interact with CENP-C and Sp100, respectively) are present in a proportion of both ND10 and interphase centromeres. Furthermore, the proteasome inhibitor MG132 induced an association between centromeres and ND10 proteins PML and Sp100 in a significant number of cells in the G(2) phase of the cell cycle. These results imply that there is a dynamic, cell cycle regulated connection between centromeres and ND10 proteins which can be stabilised by inhibition of proteasome-mediated proteolysis.

Links

PubMed

Keywords

Adaptor Proteins, Signal Transducing; Antigens, Nuclear; Autoantigens/analysis; Autoantigens/metabolism; Carrier Proteins/analysis; Carrier Proteins/metabolism; Cell Cycle/physiology; Cell Cycle Proteins/analysis; Cell Cycle Proteins/metabolism; Centromere/drug effects; Centromere/physiology; Centromere/ultrastructure; Chromosomal Proteins, Non-Histone/analysis; Chromosomal Proteins, Non-Histone/metabolism; Cysteine Endopeptidases/metabolism; Cysteine Proteinase Inhibitors/pharmacology; Hot Temperature; Humans; Interferon-alpha/pharmacology; Intracellular Signaling Peptides and Proteins; Leupeptins/pharmacology; Multienzyme Complexes/metabolism; Nuclear Proteins/analysis; Nuclear Proteins/metabolism; Proteasome Endopeptidase Complex; Recombinant Proteins/analysis; Recombinant Proteins/metabolism; SUMO-1 Protein; Transfection; Tumor Cells, Cultured; Ubiquitins/analysis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:DAXX

part_of

GO:0000775: chromosome, centromeric region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DAXX

GO:0000775: chromosome, centromeric region

ECO:0000314:

C

Fig.1

complete
CACAO 7328

HUMAN:CBX3

GO:0000775: chromosome, centromeric region

ECO:0000314:

C

Fig.1

complete
CACAO 7329

HUMAN:CBX3

part_of

GO:0000775: chromosome, centromeric region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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