The ubiquitously expressed bZIP inhibitor, JDP2, suppresses the transcription of its homologue immediate early gene counterpart, ATF3

JDP2 is a ubiquitously expressed bZIP repressor protein. JDP2 binds TPA response element and cyclic AMP response element located within various promoters. JDP2 displays a high degree of homology to the immediate early gene ATF3. ATF3 plays a crucial role in the cellular adaptive response to multiple stress insults as well as growth stimuli. We have identified ATF3 as a potential target gene for JDP2 repression. JDP2 regulates the ATF3 promoter potentially through binding to both the consensus ATF/CRE site and a non-consensus ATF3 auto-repression DNA-binding element. Expression of ATF3 protein in wild-type mouse embryo fibroblast (MEF) cells is below the detectable levels, whereas, JDP2 disrupted MEF cells display noticeable level of ATF3 protein. Following either serum or ER stress stimulation, ATF3 expression is potentiated in JDP2-KO fibroblast cells as compared with wild-type cells. Mice with either JDP2 over-expression or JDP2 disruption display undetectable level of ATF3 protein. However, ATF3 induction in response to either growth or stress signals is dependent on JDP2 expression level. ATF3 induction is attenuated in JDP2 over-expressing mice whereas is potentiated in JDP2-KO mice as compared with the corresponding wild-type mice. Collectively, the data presented strongly suggest that JDP2 plays a role in the determination of the ATF3 adaptive cellular threshold response to different stress insults and growth stimuli

Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2) involves downregulation of cyclin-A2

We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2-knockout (Jdp2KO) mice by targeting exon-1 to disrupt the site of initiation of transcription. The epidermal thickening of skin from the Jdp2KO mice after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) proceeded more rapidly than that of control mice, and more proliferating cells were found at the epidermis. Fibroblasts derived from embryos of Jdp2KO mice proliferated faster and formed more colonies than fibroblasts from wild-type mice. JDP2 was recruited to the promoter of the gene for cyclin-A2 (ccna2) at the AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin-A2 mRNA. Furthermore, reintroduction of JDP2 resulted in the repression of transcription of ccna2 and of cell-cycle progression. Thus, transcription of the gene for cyclin-A2 appears to be a direct target of JDP2 in the suppression of cell proliferation

Adverse effects of extra-articular corticosteroid injections: a systematic review

<p>Abstract</p> <p>Background</p> <p>To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection.</p> <p>Methods</p> <p>A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention).</p> <p>Results</p> <p>The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting.</p> <p>Conclusion</p> <p>In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported.</p

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD