The c-Jun Dimerization Protein 2 Inhibits Cell Transformation and Acts as a Tumor Suppressor Gene

Heinrich, Ronit; Livne, Erella; Ben-Izhak, O; Aronheim, Ami

doi:10.1074/jbc.m307608200

Cited by 66 publications

(64 citation statements)

References 27 publications

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“…1. Transcriptional analysis and co-transfection experiments strongly suggest that the primary mechanism by which overexpression of EGR-1 modulate AP-1 and NF-κB activities involves the activation of the member of the two families of the earlier proteins such as Jun and Fos (45,46). The partial inhibition by cisplatin in the transcriptional activity of the NF-κB, and the increasing activating of AP-1 in both LNCaP and PC-3 cells suggested different roles of AP-1 and NF-κB in cells overexpressing EGR-1.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of EGR-1 modulates the activity of NF-κB and AP-1 in prostate carcinoma PC-3 and LNCaP cell lines

Parra

Ferreira²,

Ortega³

2011

Int J Oncol

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Abstract. To address elements that might uniquely characterize EGR-1 mediated signaling, the expression of two transcription factors, namely, nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) were studied. PC-3 and LNCaP prostate carcinoma cell lines were transiently transfected with wildtype Egr-1 expression plasmid (pCMV-Egr-1) and treated with cisplatin and TPA. Overexpression of EGR-1 was found to induce nuclear expression of both, NF-κB and AP1. However, the intensity of the induced AP-1 and NF-κB was diminished after cisplatin treatment, but not after TPA. Our findings confirm that the overexpression of wild-type Egr-1 caused a marked increase in cell proliferation in PC-3 and LNCaP proliferation in a 14-day soft agar colony forming assay. In addition, luciferase reporter gene assay showed that the transcriptional activity of AP-1 and NF-κB in PC-3 and LNCaP prostate carcinoma cell lines was also modulated by the overexpression of EGR-1 in these cells using tandem repeated Luc-AP-1 and Luc-NF-κB. The activation of both NF-κB and AP-1 are key steps in the cascade of events following the activation of the EGR-1 gene. It was revealed that overexpression of EGR-1 selectively increased AP-1 and NF-κB activation, and that the activation of these nuclear factors appears to be essential for the induction of proliferation and anchorage independence in activated PC-3 and LNCaP cells. However, the mechanism underlying the modulation of AP-1 and NF-κB by the overexpression of EGR-1 is still unknown.

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Section: Discussionmentioning

confidence: 99%

Overexpression of EGR-1 modulates the activity of NF-κB and AP-1 in prostate carcinoma PC-3 and LNCaP cell lines

Parra

Ferreira²,

Ortega³

2011

Int J Oncol

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“…JDP2 has effects on various cellular processes. It mediates the differentiation of myoblasts [5] and osteoclasts [6], inhibits the differentiation of adipocytes [7] and embryonic carcinoma cells [8], acts as a tumor suppressor in NIH3T3 cells and prostate cancer cell lines [9], induces the partial transformation of chick embryonic fibroblasts [10], and functions as a cell-survival protein [11] and as a progesterone receptor coactivator [12]. The mechanisms of JDP2-mediated transcriptional repression may include the regulation of nucleosome assembly and histone acetylation [13].…”

Section: Introductionmentioning

confidence: 99%

IRF2‐binding protein‐1 is a JDP2 ubiquitin ligase and an inhibitor of ATF2‐dependent transcription

Kimura¹

2008

FEBS Letters

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Jun-dimerization protein 2 (JDP2) is a member of the activating protein-1 (AP-1) family of transcription factors. JDP2 dimerizes with other AP-1 proteins such as activating transcription factor-2 (ATF2) and Jun to repress transcription from promoters that contain a cyclic AMP-responsive element (CRE). Interferon regulatory factor-2-binding protein-1 (IRF2-BP1), which is reported to be a transcriptional corepressor of IRF2, was isolated as a JDP2-binding protein using an epitope-tagging method. As anticipated from the presence of a RING-finger domain, IRF2-BP1 enhanced the polyubiquitination of JDP2. Moreover, IRF2-BP1 repressed ATF2-mediated transcriptional activation from a CRE-containing promoter.

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“…[14][15][16] JDP2 can function not only as a transcriptional repressor but also as a coactivator in various types of cell, 15,[17][18][19][20] and it is involved in a variety of biological phenomena such as proliferation and differentiation of cells and apoptosis. 14,15,17,18,[20][21][22] For example, forced expression of JDP2 represses the retinoic acid-mediated (RA-mediated) transcription of the c-jun gene and the differentiation of F9 cells in response to RA. 18 By contrast, the expression of an exogenous gene for JDP2 promotes the formation of C2 myotube and strong expression of major myogenic markers in C2 myoblasts.…”

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confidence: 99%

JDP2 suppresses adipocyte differentiation by regulating histone acetylation

Nakade¹,

Pan²,

Yoshiki

et al. 2007

Cell Death Differ

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Among the events that control cellular differentiation, the acetylation of histones plays a critical role in the regulation of transcription and the modification of chromatin. Jun dimerization protein 2 (JDP2), a member of the AP-1 family, is an inhibitor of such acetylation and contributes to the maintenance of chromatin structure. In an examination of Jdp2 'knock-out' (KO) mice, we observed elevated numbers of white adipocytes and significant accumulation of lipid in the adipose tissue in sections of scapulae. In addition, mouse embryo fibroblasts (MEFs) from Jdp2 KO mice were more susceptible to adipocyte differentiation in response to hormonal induction and members of the CCAAT/enhancer-binding proteins (C/EBP) gene family were expressed at levels higher than MEFs from wild-type mice. Furthermore, JDP2 inhibited both the acetylation of histone H3 in the promoter of the gene for C/EBPd and transcription from this promoter. Our data indicate that JDP2 plays a key role as a repressor of adipocyte differentiation by regulating the expression of the gene for C/EBPd via inhibition of histone acetylation.

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The c-Jun Dimerization Protein 2 Inhibits Cell Transformation and Acts as a Tumor Suppressor Gene

Cited by 66 publications

References 27 publications

Overexpression of EGR-1 modulates the activity of NF-κB and AP-1 in prostate carcinoma PC-3 and LNCaP cell lines

Overexpression of EGR-1 modulates the activity of NF-κB and AP-1 in prostate carcinoma PC-3 and LNCaP cell lines

IRF2‐binding protein‐1 is a JDP2 ubiquitin ligase and an inhibitor of ATF2‐dependent transcription

JDP2 suppresses adipocyte differentiation by regulating histone acetylation

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