The CCN3 gene coding for an extracellular adhesion-related protein is transcriptionally activated by the p53 tumor suppressor.
The CCN3 protein (Nov, Nephroblastoma overexpressed) is a member of the CCN family (Cyr61, CTGF, Nov) of growth regulators and exerts antiproliferative properties. We show here that the tumor suppressor p53 transcriptionally upregulates the CCN3 gene. p53 is an important transcription factor contributing to cell cycle arrest and apoptosis after cell damage through the regulation of numerous target genes. We show that CCN3 mRNA and protein are upregulated following p53 expression. A DNA binding-deficient p53 mutant fails to regulate CCN3. CCN3 protein is located in the perinuclear space after induction and is also exported to the extracellular matrix. Furthermore, the CCN3 promoter is inducible by p53 and the response element is located in the first exon of the CCN3 gene. Chromatin immunoprecipitations show that p53 binds to the CCN3 promoter in vivo. As CCN3 was shown to inhibit cell growth, transcriptional induction by p53 may serve as an antiproliferative signal in the extracellular matrix. Furthermore, CCN3 depletion was also reported to reduce collagen type IV-dependent adhesion of melanocytes. Thus, elevated levels of CCN3 protein regulated by p53 might influence cell adhesion.
Böhlig
Levin
L
Universitätsfrauenklinik Leipzig, Universität Leipzig, Germany.
Metzger
Roman
R
Rother
Karen
K
Till
Holger
H
Engeland
Kurt
K
D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D024141:Collagen Type IV / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D055514:Nephroblastoma Overexpressed Protein; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
C526317:CCN2 protein, human; C526319:CCN3 protein, human; D024141:Collagen Type IV; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D055513:Connective Tissue Growth Factor