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PMID: 12374749 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

SSRP1 functions as a co-activator of the transcriptional activator p63.

The EMBO journal ·Vol. 21 ·No. 20 ·2002-10-15 ·Pages 5487-97

Zeng SX, Dai MS, Keller DM, Lu H

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.

MeSH Terms
Animals Apoptosis Binding Sites Cell Line Cyclin-Dependent Kinase Inhibitor p21 Cyclins/genetics DNA-Binding Proteins/genetics,metabolism G1 Phase Gene Deletion Genes, Tumor Suppressor High Mobility Group Proteins/genetics,metabolism Humans Luciferases/genetics Membrane Proteins Mice Nuclear Proteins Phosphoproteins/chemistry,genetics,metabolism Promoter Regions, Genetic Protein Structure, Tertiary Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-mdm2 Recombinant Proteins/chemistry,genetics,metabolism Trans-Activators/chemistry,genetics,metabolism Transcription Factors Transcriptional Elongation Factors Tumor Suppressor Protein p53/genetics,metabolism Tumor Suppressor Proteins
Chemicals
CDKN1A protein, human CKAP4 protein, human Cdkn1a protein, mouse Cyclin-Dependent Kinase Inhibitor p21 Cyclins DNA-Binding Proteins High Mobility Group Proteins Membrane Proteins Nuclear Proteins Phosphoproteins Proto-Oncogene Proteins Recombinant Proteins SSRP1 protein, human TP63 protein, human Trans-Activators Transcription Factors Transcriptional Elongation Factors Trp63 protein, mouse Tumor Suppressor Protein p53 Tumor Suppressor Proteins Ssrp1 protein, mouse Luciferases MDM2 protein, human Mdm2 protein, mouse Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zeng Shelya X
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA.
Dai Mu-Shui
Keller David M
Lu Hua
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf540
Published
2002-10-15
Pages
5487-97
Language
English
Region
England
NLM ID
8208664
PMCID
PMC129072
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1093/emboj/cdf540 PMC Full Text View journal details
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