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PMID:15282309

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Citation

King, FW and Shtivelman, E (2004) Inhibition of nuclear import by the proapoptotic protein CC3. Mol. Cell. Biol. 24:7091-101

Abstract

We report here that the normal cellular protein CC3/TIP30, when in excess, inhibits nuclear import in vitro and in vivo. CC3 binds directly to the karyopherins of the importin beta family in a RanGTP-insensitive manner and associates with nucleoporins in vivo. CC3 inhibits the nuclear import of proteins possessing either the classical nuclear localization signal or the M9 signal recognized by transportin. CC3 also inhibits nuclear translocation of transportin itself. Cells modified to express higher levels of CC3 have a slower rate of nuclear import and, as described earlier, show an increased sensitivity to death signals. A mutant CC3 protein lacking proapoptotic activity has a lower affinity for transportin, is displaced from it by RanGTP, and fails to inhibit nuclear import in vitro and in vivo. Together, our results support a correlation between the ability of CC3 to form a RanGTP-resistant complex with importins, inhibit nuclear import, and induce apoptosis. Significantly, a dominant-negative form of importin beta1 shown previously to inhibit multiple transport pathways induces rapid cell death, strongly indicating that inhibition of nuclear transport serves as a potent apoptotic signal.

Links

PubMed PMC479715 Online version:10.1128/MCB.24.16.7091-7101.2004

Keywords

Acetyltransferases/genetics; Acetyltransferases/metabolism; Active Transport, Cell Nucleus/physiology; Apoptosis/physiology; Cell Line, Tumor; Humans; Karyopherins/genetics; Karyopherins/metabolism; Nuclear Localization Signals; Nuclear Pore/metabolism; Protein Binding; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; ran GTP-Binding Protein/metabolism

Significance

Annotations

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

HUMAN:IPO5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BUP3

F

Seeded From UniProt

complete

HUMAN:IPO7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BUP3

F

Seeded From UniProt

complete

HUMAN:IMB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BUP3

F

Seeded From UniProt

complete

HUMAN:IPO9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BUP3

F

Seeded From UniProt

complete

HUMAN:HTAI2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9C0E2

F

Seeded From UniProt

complete

HUMAN:HTAI2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14974

F

Seeded From UniProt

complete

HUMAN:HTAI2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96P70

F

Seeded From UniProt

complete

HUMAN:HTAI2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O95373

F

Seeded From UniProt

complete

HUMAN:HTAI2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00410

F

Seeded From UniProt

complete

HUMAN:HTAI2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HTAI2

located_in

GO:0005635: nuclear envelope

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:XPO4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BUP3

F

Seeded From UniProt

complete

HUMAN:HTAI2

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HTAI2

part_of

GO:0005635: nuclear envelope

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:HTAI2

involved_in

GO:0051170: import into nucleus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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