Abstract
The p53 homolog p63 is a transcriptional activator. Here, we describe the identification of an HMG1-like protein SSRP1 as a co-activator of p63. Over expression of wild-type, but not deletion mutant, SSRP1 remarkably enhanced p63gamma-dependent luciferase activity, G1 arrest, apoptosis and expression of endogenous PIG3, p21(Waf1/cip1) and MDM2 in human p53-deficient lung carcinoma H1299 cells and mouse embryonic fibroblasts. Also, SSRP1 interacted to p63gamma in vitro and in cells, and resided with p63gamma at the p53-responsive DNA element sites of the cellular endogenous MDM2 and p21(Waf1/cip1) promoters. Moreover, N-terminus-deleted p63 (DeltaN-p63) bound to neither SSRP1 nor its central domain in vitro. Accordingly, SSRP1 was unable to stimulate DeltaN-p63-mediated residual luciferase activity and apoptosis in cells. Finally, the ectopic expression of the central p63-binding domain of SSRP1 inhibited p63-dependent transcription in cells. Thus, these results suggest that SSRP1 stimulates p63 activity by associating with this activator at the promoter.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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Binding Sites
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Cell Line
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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G1 Phase
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Gene Deletion
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Genes, Tumor Suppressor
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High Mobility Group Proteins / genetics
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High Mobility Group Proteins / metabolism*
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Humans
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Luciferases / genetics
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Membrane Proteins*
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Mice
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Nuclear Proteins*
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Phosphoproteins / chemistry
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Promoter Regions, Genetic
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-mdm2
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors
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Transcriptional Elongation Factors*
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Proteins
Substances
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CDKN1A protein, human
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CKAP4 protein, human
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA-Binding Proteins
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High Mobility Group Proteins
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Membrane Proteins
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Nuclear Proteins
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Phosphoproteins
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Proto-Oncogene Proteins
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Recombinant Proteins
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SSRP1 protein, human
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TP63 protein, human
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Trans-Activators
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Transcription Factors
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Transcriptional Elongation Factors
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Trp63 protein, mouse
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Ssrp1 protein, mouse
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Luciferases
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MDM2 protein, human
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Mdm2 protein, mouse
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Proto-Oncogene Proteins c-mdm2