Suppression of cell cycle progression by Jun dimerization protein (JDP2) involves down-regulation of cyclin A2

Pan, Jianzhi; Nakade, Koji; Masuzaki, Satoko; Hasegawa, Hitomi; Huang, Ying‐Fong; Murata, Takehide; Yoshiki, Atsushi; Yamaguchi, Naoto; Obata, Yuichi; Yokoyama, Kazunari K.

doi:10.1038/npre.2009.3840.1

Cited by 4 publications

(3 citation statements)

References 40 publications

(47 reference statements)

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“…It is well established that JDP2 counteracts AP-1 (activator protein 1) transcription [1], and thus may interfere with the oncogenic properties of c-Jun and ATF2. JDP2 has been found to inhibit cell proliferation [9] and cell transformation induced by Ras in vitro and in xenografts injected into SCID (severe combined immunodeficiency) mice [10]; on the other hand, it has been identified as a candidate oncogene in a highthroughput screen based on viral insertional mutagenesis in mice [11][12][13]. In addition, JDP2 overexpression potentiates hepatocellular carcinoma in mice [14].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of JDP2 on threonine-148 by the c-Jun N-terminal kinase targets it for proteosomal degradation

Weidenfeld-Baranboim

Koren

Aronheim

2011

Biochemical Journal

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JDP2 (c-Jun dimerization protein 2) is a member of the basic leucine zipper family of transcription factors that is ubiquitously expressed in all examined cell types. JDP2 is phosphorylated on Thr148 by JNK (c-Jun N-terminal kinase) and p38 kinase, although the functional role of its phosphorylation is unknown. In the present paper we show that the JDP2 protein level is dramatically reduced in response to serum stimulation, anisomycin treatment, ultraviolet light irradiation and cycloheximide treatment, all of which activate the JNK pathway. In addition, endogenous and overexpressed JDP2 are phosphorylated in response to these stimuli. Replacement of Thr148 with an alanine residue stabilizes ectopically expressed JDP2 in the presence of the stimuli; conversely, substitution with glutamic acid destabilizes it. Serum-induced phosphorylation and degradation of JDP2 are specific to JNK activation since a JNK inhibitor (SP600125) abolishes these effects, whereas p38 and MEK inhibitors (SB203580 and UO126) have no effect. In the presence of cycloheximide, JDP2 is rapidly phosphorylated and degraded due to the combined effects of protein synthesis inhibition and activation of JNK. Pre-treatment of cells with SP600125 prior to cycloheximide treatment significantly prolongs the half-life of JDP2 that is found mainly in the unphosphorylated form. Lastly, the proteasome inhibitor (MG132) rescues JDP2 degradation following cycloheximide treatment and increases the expression of the JDP2 phospho-mimetic T148E mutant. Collectively, these results suggest that phosphorylation of JDP2 on thr148 by JNK targets it to the proteasome for degradation.

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Section: Introductionmentioning

confidence: 99%

Phosphorylation of JDP2 on threonine-148 by the c-Jun N-terminal kinase targets it for proteosomal degradation

Weidenfeld-Baranboim

Koren

Aronheim

2011

Biochemical Journal

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“…Class B contains three genes including gene JDP2, TP53INP2 and DDX5. Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription which is associated with suppression of cycle progression by the gene JDP2 (Pan et al, 2010). The TP53INP2 is related to the death receptor signaling (Ivanova and Zorzano, 2019).…”

Section: Gene Annotations For 30 Survival-related Genes In Three Cancersmentioning

confidence: 99%

Two-variate phenotype-targeted tests for detecting phenotypic biomarkers in cancers

2020

IJDMB

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Detection of cancer-related phenotypic biomarkers is crucial for clinical research. Traditional pipeline consists of two stages, i.e., candidates are first selected to be significantly differentially expressed between tumouradjacent and tumour conditions, and then later are filtered by Phenotype-Targeted tests (PT tests). Such two-phase process has low-detection power. In this paper, two-variate PT test, which jointly considers tumour-adjacent data and tumour data, is adopted to strengthen the detection power. We conduct a systematic investigation on the three implementations of two-variate PT tests for detecting phenotypic biomarkers in three types of cancers, and provide a practical guideline for the usage of the two-variate PT tests. Experimental analysis indicates that the two-variate PT tests achieve stronger detection power than traditional methods. The tumour-adjacent data provides complementary information to the discriminant analysis, and Fisher discriminant analysis is able to best implement two-variate PT test for detecting phenotypic biomarkers in cancers.

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“…Our findings also provide new insights into the molecular mechanisms, by which senescence is induced in the context of the epigenetic regulation of the p16 Ink4a / Arf locus. Recently, we reported that JDP2 regulates the expressions of cell-cycle regulators such as cyclin A2, cyclin E2, and p16 Ink4a and also affects the expression of p53 and p21 protein [ 120 ]. Thus, it is evident that JDP2 control the expression of cell-cycle regulators to induce the cell-cycle arrest via p53-p21 pathway and RB-p16 pathway.…”

Section: Mechanism Of Jdp2-mediated Regulation Of C/ebp mentioning

confidence: 99%

Jun Dimerization Protein 2 Controls Senescence and Differentiation via Regulating Histone Modification

Huang

Hasegawa

Wang

et al. 2010

BioMed Research International

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Transcription factor, Jun dimerization protein 2 (JDP2), binds directly to histones and DNAs and then inhibits the p300-mediated acetylation both of core histones and of reconstituted nucleosomes that contain JDP2 recognition DNA sequences. JDP2 plays a key role as a repressor of adipocyte differentiation by regulation of the expression of the gene C/EBPδ via inhibition of histone acetylation. Moreover, JDP2-deficient mouse embryonic fibroblasts (JDP2−/− MEFs) are resistant to replicative senescence. JDP2 inhibits the recruitment of polycomb repressive complexes (PRC1 and PRC2) to the promoter of the gene encoding p16Ink4a, resulting from the inhibition of methylation of lysine 27 of histone H3 (H3K27). Therefore, it seems that chromatin-remodeling factors, including the PRC complex controlled by JDP2, may be important players in the senescence program. The novel mechanisms that underline the action of JDP2 in inducing cellular senescence and suppressing adipocyte differentiation are reviewed.

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Suppression of cell cycle progression by Jun dimerization protein (JDP2) involves down-regulation of cyclin A2

Cited by 4 publications

References 40 publications

Phosphorylation of JDP2 on threonine-148 by the c-Jun N-terminal kinase targets it for proteosomal degradation

Phosphorylation of JDP2 on threonine-148 by the c-Jun N-terminal kinase targets it for proteosomal degradation

Two-variate phenotype-targeted tests for detecting phenotypic biomarkers in cancers

Jun Dimerization Protein 2 Controls Senescence and Differentiation via Regulating Histone Modification

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