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PMID:9230084

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Citation

Sternsdorf, T, Jensen, K, Züchner, D and Will, H (1997) Cellular localization, expression, and structure of the nuclear dot protein 52. J. Cell Biol. 138:435-48

Abstract

Nuclear dots containing PML and Sp100 proteins (NDs) play a role in the development of acute promyelocytic leukemia, are modified after infection with various viruses, and are autoimmunogenic in patients with primary biliary cirrhosis (PBC). PML and Sp100 gene expression is strongly enhanced by interferons (IFN). Based on immunostaining with a monoclonal antibody (mAb C8A2), a third protein, nuclear dot protein 52 (NDP52), was recently localized in NDs. Here we analyzed the cellular localization, expression, and structure of NDP52 in more detail. Our NDP52-specific sera revealed mainly cytoplasmic staining but no ND pattern, neither in untreated nor in IFN-treated cells. Cells transfected with NDP52 expression vectors showed exclusively cytoplasmic staining. In subcellular fractionation experiments, NDP52 was found in cytoplasmic and nuclear fractions. Unlike as described for Sp100 and PML, NDP52 mRNA and protein levels were only marginally enhanced by IFN gamma and not enhanced at all by IFN beta. NDP52 homodimerization but no heterodimerization with Sp100 or PML could be demonstrated. None of the 93 PBC sera tested contained autoantibodies against NDP52. Finally, mAb C8A2 reacted not only with NDP52 but also with a conformation-dependent epitope on the Sp100 protein. These data imply that NDP52 forms homodimers but no heterodimers with Sp100 and PML, lacks autoantigenicity in PBC, localizes mainly in the cytoplasm, and is associated with the nucleus, but not with NDs. Finally, unlike Sp100 and PML, NDP52 expression is neither markedly enhanced nor localization detectably altered by type I and II IFNs.

Links

PubMed PMC2138200

Keywords

Animals; Antibodies, Monoclonal; Antigens, Nuclear; Autoantibodies/blood; Autoantigens/metabolism; Cell Line; Cell Nucleus/chemistry; Cloning, Molecular; Cross Reactions; Cytoplasm/chemistry; DNA, Complementary/genetics; Dimerization; Gene Expression; HeLa Cells; Humans; Interferon-beta/pharmacology; Interferon-gamma/pharmacology; Liver Cirrhosis, Biliary/immunology; Neoplasm Proteins; Nuclear Proteins/analysis; Nuclear Proteins/chemistry; Nuclear Proteins/metabolism; RNA, Messenger/analysis; Rats; Sequence Analysis, DNA; Transcription Factors/metabolism; Tumor Suppressor Proteins

Significance

Annotations

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

HUMAN:SP100

involved_in

GO:0034341: response to interferon-gamma

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SP100

involved_in

GO:0034340: response to type I interferon

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SP100

located_in

GO:0016605: PML body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PML

located_in

GO:0016605: PML body

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CACO2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CACO2

involved_in

GO:0034341: response to interferon-gamma

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CACO2

located_in

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CACO2

enables

GO:0042803: protein homodimerization activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13137

F

Seeded From UniProt

complete

HUMAN:PML

part_of

GO:0016605: PML body

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PML

enables

GO:0042803: protein homodimerization activity

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P29590

F

Seeded From UniProt

complete

See also

References

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