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PMID:14729977

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Citation

Bergamaschi, D, Samuels, Y, Jin, B, Duraisingham, S, Crook, T and Lu, X (2004) ASPP1 and ASPP2: common activators of p53 family members. Mol. Cell. Biol. 24:1341-50

Abstract

We recently showed that ASPP1 and ASPP2 stimulate the apoptotic function of p53. We show here that ASPP1 and ASPP2 also induce apoptosis independently of p53. By binding to p63 and p73 in vitro and in vivo, ASPP1 and ASPP2 stimulate the transactivation function of p63 and p73 on the promoters of Bax, PIG3, and PUMA but not mdm2 or p21(WAF-1/CIP1). The expression of ASPP1 and ASPP2 also enhances the apoptotic function of p63 and p73 by selectively inducing the expression of endogenous p53 target genes, such as PIG3 and PUMA, but not mdm2 or p21(WAF-1/CIP1). Removal of endogenous p63 or p73 with RNA interference demonstrated that (16) the p53-independent apoptotic function of ASPP1 and ASPP2 is mediated mainly by p63 and p73. Hence, ASPP1 and ASPP2 are the first two identified common activators of all p53 family members. All these results suggest that ASPP1 and ASPP2 could suppress tumor growth even in tumors expressing mutant p53.

Links

PubMed PMC321425

Keywords

Amino Acid Sequence; Apoptosis/physiology; Apoptosis Regulatory Proteins; Carrier Proteins/metabolism; DNA-Binding Proteins/metabolism; Genes, Tumor Suppressor; Intracellular Signaling Peptides and Proteins; Molecular Sequence Data; Multigene Family; Nuclear Proteins/metabolism; Phosphoproteins/metabolism; Promoter Regions, Genetic; Trans-Activators/metabolism; Tumor Suppressor Protein p53/metabolism; Tumor Suppressor Proteins

Significance

Annotations

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

HUMAN:P73

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13625

F

Seeded From UniProt

complete

HUMAN:P73

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:O15350

F

Seeded From UniProt

complete

HUMAN:ASPP2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H3D4

F

Seeded From UniProt

complete

HUMAN:ASPP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H3D4

F

Seeded From UniProt

complete

HUMAN:ASPP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O15350

F

Seeded From UniProt

complete

HUMAN:ASPP1

involved_in

GO:0045786: negative regulation of cell cycle

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

P

Seeded From UniProt

complete

HUMAN:P63

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13625

F

Seeded From UniProt

complete

HUMAN:P63

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96KQ4

F

Seeded From UniProt

complete

HUMAN:ASPP2

involved_in

GO:0045786: negative regulation of cell cycle

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

P

Seeded From UniProt

complete


See also

References

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