Multiple functions of the histone chaperone Jun dimerization protein 2

Abstract

The Jun dimerization protein 2 (JDP2) is part of the family of stress-responsible transcription factors such as the activation protein-1, and binds the 12-O-tetradecanoylphorbol-13-acetateresponse element and the cAMP response element. It also plays a role as a histone chaperone and participates in diverse processes, such as cell-cycle arrest, cell differentiation, apoptosis, senescence, and metastatic spread, and functions as an oncogene and anti-oncogene, and as a cellular reprogramming factor. However, the molecular mechanisms underlying these multiple functions of JDP2 have not been clarified. This review summarizes the structure and function of JDP2, highlighting the specific role of JDP2 in cellular-stress regulation and prevention.

Keywords: AP-1 repressor; ARE; Function; Histone chaperone; JDP2; ROS; Structure.

Fig. 1.

Schematic domain structure of Jun dimerization protein 2. The models of three Jun dimerization protein 2 (JDP2) isoforms such as canonical protein (163 amino acids) and isoform 2 (174 amino acids) and isoform 3 (134 amino acids) were presented [http://www.ncbi.nlm.nih.gov/gene/122953 LocusLink Report (LocusID: 122953), Aronheim et al., 1997; Jin et al., 2001; Kawaida et al., 2003]. The histone binding, basic region and leucine zipper region were listed (Jin et al., 2006). The first to fourth leucine zipper regions are L–L type and the 5^th zipper region is L–H type.

Fig. 2.

Schematic representation of the role of JDP2 on oxidative stress and antioxidation. Various stresses regulate the expression of JDP2. JDP2 associates with sMaf family and Nrf2 to induce the ARE response of variety of antioxidation response related genes, and at the same time JDP2 inhibits the ROS production to maintain the ROS homeostasis against oxidative stress (Tanigawa et al., 2013; Tanigawa and Yokoyama, 2013). ROS are generated by the oxidation of lipid and DNA via ER stress. Therefore, JDP2 controls the balance of ROS production through the transcriptional control with respective partner molecules for cytoprotection.

Fig. 3.

Putative models of JDP2 to play the double-edge swords to control the transcription and epigenetic regulation. Possible positive and negative transcriptional regulations of JDP2 are presented in this model. JDP2 might form the complex with sMafK and/or Nrf2 and bind to the ARE element to increase the transcription of ARE related genes (Tanigawa et al., 2013) via recruitment of CBP/p300 coactivator-dependent Nrf2 acetylation (Kawai et al., 2011) or possibly histone acetylation. On the other hand, JDP2 might recruit the HDAC family (Jin et al., 2002; Darlyuk-Saadon et al., 2012; Maruyama et al., 2012) or INHAT activity (Jin et al., 2006) to repress the transcription of cell cycle related genes (Pan et al., 2010).