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PMID:11684014

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Citation

Samuels-Lev, Y, O'Connor, DJ, Bergamaschi, D, Trigiante, G, Hsieh, JK, Zhong, S, Campargue, I, Naumovski, L, Crook, T and Lu, X (2001) ASPP proteins specifically stimulate the apoptotic function of p53. Mol. Cell 8:781-94

Abstract

We identified a family of proteins termed ASPP. ASPP1 is a protein homologous to 53BP2, the C-terminal half of ASPP2. ASPP proteins interact with p53 and specifically enhance p53-induced apoptosis but not cell cycle arrest. Inhibition of endogenous ASPP function suppresses the apoptotic function of endogenous p53 in response to apoptotic stimuli. ASPP enhance the DNA binding and transactivation function of p53 on the promoters of proapoptotic genes in vivo. Two tumor-derived p53 mutants with reduced apoptotic function were defective in cooperating with ASPP in apoptosis induction. The expression of ASPP is frequently downregulated in human breast carcinomas expressing wild-type p53 but not mutant p53. Therefore, ASPP regulate the tumor suppression function of p53 in vivo.

Links

PubMed

Keywords

Apoptosis/genetics; Apoptosis/physiology; Apoptosis Regulatory Proteins; Breast Neoplasms; Carcinoma; Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Separation; Cyclin-Dependent Kinase Inhibitor p21; Cyclins/genetics; Female; Flow Cytometry; Humans; Microscopy, Fluorescence; Molecular Sequence Data; Peptide Fragments/genetics; Peptide Fragments/metabolism; Promoter Regions, Genetic/genetics; Protein Structure, Tertiary; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins c-bcl-2; Transcriptional Activation/genetics; Tumor Cells, Cultured; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism; bcl-2-Associated X Protein

Significance

Annotations

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

HUMAN:P53

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13625

F

Seeded From UniProt

complete

HUMAN:P53

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96KQ4

F

Seeded From UniProt

complete

HUMAN:ASPP2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04637

F

Seeded From UniProt

complete

HUMAN:ASPP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04637

F

Seeded From UniProt

complete

HUMAN:ASPP1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ASPP1

involved_in

GO:0072332: intrinsic apoptotic signaling pathway by p53 class mediator

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BCL2

involved_in

GO:2001243: negative regulation of intrinsic apoptotic signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ASPP2

involved_in

GO:0072332: intrinsic apoptotic signaling pathway by p53 class mediator

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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