TRE-dependent transcription activation by JDP2-CHOP10 association

Abstract

The c-Jun dimerization protein 2, JDP2, is a member of the activating protein 1 (AP-1) family of transcription factors. Overexpression of JDP2 has been shown to result in repression of AP-1-dependent transcription and inhibition of cellular transformation. Other studies suggested that JDP2 may function as an oncogene. Here we describe the identification of CHOP10, a member of the CCAAT enhancer binding proteins, as a protein associating with JDP2. In contrast to the inhibition of transcription by JDP2, JDP2–CHOP complex strongly enhances transcription from promoters containing TPA response elements (TRE), but not from those containing cyclic AMP response elements (CRE). The association between JDP2 and CHOP10 involves the leucine zipper motifs of both proteins, whereas, the basic domain of CHOP10 contributes to the association of the JDP2–CHOP10 complex with the DNA. DNA binding of JDP2–CHOP complex is observed both in vitro and in vivo. Finally, overexpression of JDP2 results in increased cell viability following ER stress and counteracts CHOP10 pro-apoptotic activity. JDP2 expression may determine the threshold for cell sensitivity to ER stress. This is the first report describing TRE-dependent activation of transcription by JDP2 and thus may provide an explanation for the as yet unexplored oncogenic properties of JDP2.

ATF3-dependent cross-talk between cardiomyocytes and macrophages promotes cardiac maladaptive remodeling

“…ATF3 typically dampens the response by functioning as a negative regulator and repressing transcription. However, ATF3 may act as an activator in different cellular contexts [36] and through the association with different protein partners [23]. We used a PE infusion model aiming to mimic chronic pressure overload [7,32].…”

“…In contrast, JDP2 is constitutively expressed in all cells tested [17]. JDP2 and ATF3 are able to associate with numerous bZIP protein family members and either inhibit transcription [17,[20][21][22] or potentiate transcription depending on their interacting partner [23]. Importantly, ATF3 expression is highly induced specifically in cardiomyocytes following acute challenge with isoproterenol, PE and angiotensin II [24].…”

Involvement of Jun Dimerization Protein 2 (JDP2) in the Maintenance of Epstein-Barr Virus Latency

“…We speculate that the affinity between the repressor and those promoters might vary. Aronheim's group (26) recently demonstrated that JDP2 activates transcription from TPA responsive element-dependent promoters through association with CHOP10, suggesting that JDP2 can be a transcriptional activator, as well, depending on the context. One possible hypothesis is that the CMV promoter might be regulated both positively and negatively by JDP2, and JDP2 knockdown act in both ways, whereas exogenous overexpression causes emphatic effects on the negative side.…”

“…It has been reported that JDP2 recruits histone deacetylase 3 (HDAC3) to the promoters of target genes and inhibits histone acetyltransferase activity, thereby suppressing transcriptional activity (14,24). Depending on the context and cell type, however, it can alternatively act as a transcriptional activator (25,26).…”

Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus

“…GABBR1 immunofluorescence was determined by standard techniques using an anti-GABBR1 antibody (Novus Biologicals, Littletown). Western blot for the transcription factor HoxD10 was performed on nuclear protein extract as previously described 36, 37 . RNA was extracted from PVN micro punches or cultured cells as described in the data supplement.…”