ASPP proteins specifically stimulate the apoptotic function of p53.
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.
Samuels-Lev
Y
Y
Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
O'Connor
D J
DJ
Bergamaschi
D
D
Trigiante
G
G
Hsieh
J K
JK
Zhong
S
S
Campargue
I
I
Naumovski
L
L
Crook
T
T
Lu
X
X
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms; D002277:Carcinoma; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002469:Cell Separation; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
D051017:Apoptosis Regulatory Proteins; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C090468:TP53BP2 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein