The c-Jun dimerization protein 2 inhibits cell transformation and acts as a tumor suppressor gene.
The c-Jun dimerization protein, JDP2, is a member of the AP-1 (activating protein-1) family of the basic leucine zipper transcription factors. JDP2 can bind 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive element and cAMP-responsive element DNA response elements, resulting in the inhibition of transcription. Although the role of AP-1 in cell proliferation and malignant transformation is well established, the role of JDP2 in this process is of subject to debate. On the one hand, JDP2 was shown to inhibit cyclin D transcription and promote differentiation of skeletal muscle and osteoclast cells. On the other hand, JDP2 was shown to partially transform chicken embryo fibroblast and was identified in a screen for oncogenes able to collaborate with the loss of p27kip cyclin-dependent inhibitor to induce lymphomas. Using cell transformation assays in NIH3T3 cells and injection of prostate cancer cell lines overexpressing JDP2 into severe combined immuno-deficient (SCID) mice, we show for the first time the potential role of JDP2 in inhibition of cell transformation and tumor suppression. The mechanism of tumor suppressor action of JDP2 can be partially explained by the generation of inhibitory AP-1 complexes via the increase of JunB, JunD, and Fra2 expression and decrease of c-Jun expression.
Heinrich
Ronit
R
Department of Molecular Genetics, The B. Rappaport Institute in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Livne
Erella
E
Ben-Izhak
Offer
O
Aronheim
Ami
A
D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D002469:Cell Separation; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D056741:Cyclin D; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000378:metabolism; D041681:NIH 3T3 Cells; D010010:Osteoclasts / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D056741:Cyclin D; D016213:Cyclins; C491387:JDP2 protein, human; C491386:Jundp2 protein, mouse; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004247:DNA; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate