Our promise to you:
Guaranteed product quality, expert customer support.
The c-Jun dimerization protein 2 (JDP2) is a member of the basic leucine zipper (bZIP) superfamily, which is part of the activator protein-1 (AP-1) family. AP-1-driven genes play crucial roles in many aspects of liver carcinogenesis, including proliferation, differentiation, and reactive oxygen species (ROS) accumulation and metabolism. Some studies have showed that JDP2 forms a homodimer or a heterodimer with other Jun members to repress the transcriptional activity of the AP-1 complex. Recent studies have suggested that JDP2 may function as a tumor suppressor through its suppressive action against the AP-1 complex, which is known to drive oncogenic signals in several human malignancies. One report showed that high expression of JDP2 was signiﬁcantly correlated with smaller tumor size and early stage Hepatocellular Carcinoma (HCC). JDP2 was associated with better survival in HCC patients. This suggests that JDP2 may serve as a tumor suppressor in HCC.
JDP2 is expressed in various kinds of cells. It was originally isolated based on its association with c-Jun3, which is a component of the transcription factor AP-1, and ATF2 (activating transcription factor 2). JDP2specifically interacts with c-Jun and ATF2. JDP2 typically suppresses transcription through binding to CRE (cAMP responsive promoter element) and TRE (trans-activator response element) DNA elements found in the promoters of numerous genes by recruitment of histone deacetylases (HDACs). DNA binding was enhanced after dimerization with c-jun, but transcription was inhibited. JDP2 inhibits transcription by multiple mechanisms. Importantly, JDP2 can act as a transcriptional activator depending on the protein binding partner, specifically with the bZIP family member CHOP10 or serve as co-activator when associates with members of the steroid hormone receptor family.
JDP2 is involved in cell differentiation processes, such as adipocytes, differentiation of skeletal muscle cells and osteoclasts. Potentiation of cell differentiation is facilitated by the ability of JDP2 to induce cell cycle withdrawal. Several studies suggest that JDP2 has a dual role in malignant transformation. On the one hand, JDP2 can counteract AP-1 transcription, and thus may interfere with the oncogenic properties of c-Jun. Indeed, JDP2 expression was found to inhibit cell transformation induced by Ras in vitro and in prostate cancer xenografts injected into SCID mice. In addition, some reports showed that JDP2 suppresses cell cycle progression by down-regulation of cyclin-A2. On the other hand, JDP2 has been identified as a candidate oncogene in a high-throughput screen based on viral insertional mutagenesis in mice. Consistently, tetracycline regulated transgenic mice expressing JDP2 in liver tissue exhibited higher mortality rate and increased number and size of tumors when compared with their wild-type counterparts in hepatocellular carcinoma mouse model. Furthermore, one report showed that JDP2 expression in the host suppresses primary tumor growth. However, it promotes metastatic spread. These metastatic effects are partially mediated by BMDCs colonizing the primary tumor site and further secreting the prometastatic chemokine, CCL5.