Disease relevance of Jun

• Collectively, these studies show that c-Jun and E1A regulate basal transcription of bsp in osteosarcoma cells by recruiting the NF-Y transcriptional complex to the ICE box in a mechanism that is independent of p300/CBP and P/CAF HAT activities [1].
• In this study we examined in vitro the role of Fos/Jun protein in transcriptional regulation of the AVP gene using the BE(2)M17 neuroblastoma cell line [2].
• These results also stress the necessity of examining the composition of Fos and Jun-related antigens and the metabolic state of Fos and Jun(s) in different experimental models of nervous system injury [3].
• In addition, the expression of ASK1-KM, a dominant-negative form of ASK1, using an adenovirus system was found to inhibit the activation of p38 and c-Jun and to prevent apoptosis [4].
• Hypoxia induces selective SAPK/JNK-2-AP-1 pathway activation in the nucleus tractus solitarii of the conscious rat [5].
• These results suggest that Hcy-induced MCP-1 expression in the liver is mediated via AP-1 activation, which may contribute to chronic inflammation associated with hyperhomocysteinemia [6].

Psychiatry related information on Jun

• Thus, morphine dependence results in the alteration of diverse, brain region-specific, signal transcription pathways involving AP-1 transcription factors [7].
• This investigation tested if lithium, the primary therapeutic agent for bipolar mood disorder, modulated activation of the AP-1 transcription factor in PC12 cells treated with nerve growth factor (NGF), which induces robust responses in these cells [8].
• The results suggest that AD might mediate, at least in part, the long term effects of sleep deprivation by inducing c-Fos protein and subsequent AP1 binding [9].

High impact information on Jun

• In contrast, nitric oxide (NO) donors inhibit PKC-induced VEGF upregulation by interfering with binding of the transcription factor activator protein-1 (AP-1) to the VEGF promoter [10].
• The Fos and Jun oncoproteins form dimeric complexes that stimulate transcription of genes containing activator protein-1 regulatory elements [11].
• The data suggest that Fos and Jun dimerize via a parallel interaction of helical domains containing a heptad repeat of leucine residues (the leucine zipper) [12].
• Parallel association of Fos and Jun leucine zippers juxtaposes DNA binding domains [12].
• The protein products of the fos and jun proto-oncogenes form a heterodimeric complex that participates in a stable high affinity interaction with DNA elements containing AP-1 binding sites [12].

Chemical compound and disease context of Jun

• The activator protein-1 (AP-1) inhibitor curcumin, a polyphenolic compound derived from Curcuma longa, has been shown to reduce collagen accumulation in experimental pulmonary fibrosis [13].
• Important role of angiotensin II-mediated c-Jun NH(2)-terminal kinase activation in cardiac hypertrophy in hypertensive rats [14].
• Dominant negative mutant of c-Jun inhibits cardiomyocyte hypertrophy induced by endothelin 1 and phenylephrine [15].
• In conclusion, Ang II may activate JNK in cultured cardiac myocytes through an increase in intracellular Ca2+ and activation of protein kinase C, and the activated JNK may regulate gene expression by activating AP-1 during Ang II-induced cardiac hypertrophy [16].
• Losartan, an AT(1) receptor antagonist, prevented the onset of cardiac hypertrophy and regressed the progression of cardiac hypertrophy in SHRSP, being accompanied by the reduction of JNK activity and activator protein-1 (AP-1) activity in SHRSP [14].

Biological context of Jun

• The increase in bsp transcription did not require phosphorylation of c-Jun and was not altered by trichostatin treatment or by ectopic expression of p300/CREB-binding protein (CBP) or mutated forms lacking histone acetyltransferase (HAT) activity [1].
• Pretreatment with MAP kinase kinase inhibitor PD098059 or JNK-c-Jun/AP-1 inhibitor curcumin attenuated the H2O2-induced apoptosis [17].
• These results show that c-Fos and different Jun-related antigens are expressed following KA excitotoxicity, and that posttranslational modifications involving phosphorylation of c-Fos and Jun(s) may occur following KA injection [3].
• The vitamin E deficiency-mediated loss of AP-1 activity was not due to an alteration in the dimeric composition of constituent proteins, but rather to a general down-regulation of steady-state levels of members of the Fos and Jun families of proteins [18].
• As a possible mechanism of this synergistic action on CAM expression, hypoxia induced a time-dependent increase in the DNA binding activity of both NF-kappaB and activator protein-1 (AP-1), two transcription factors important for cell adhesion molecule expression [19].

Anatomical context of Jun

• Increased expression of endogenous c-Jun induced by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and ectopic expression of c-Jun increased basal transcription of chimeric reporter constructs encompassing the proximal promoter by 1.5-3-fold in ROS 17/2.8 osteosarcoma cells, with more modest effects in a normal bone cell line, RBMC-D8 [1].
• Therefore, we tested the hypothesis that the increase in Cx-43 mRNA levels in the myometrium during labor and after estrogen administration is mediated indirectly through induction of trans-activating factors, of which Fos and Jun are putative candidates [20].
• We investigated the mechanisms by which IL-6 induces c-Jun phosphorylation and PP2A inactivation in Rat-1 fibroblasts [21].
• Mesangial cells exposed to H2O2 undergo apoptosis via the activator protein 1 (AP-1)-dependent pathway [22].
• These results show that dietary fat type modulates the early activation of hypertrophic genes in pressure-overloaded myocardium involving the distinct activation of AP-1 and MAPK signal transduction pathways [23].

Associations of Jun with chemical compounds

• Coexpression of the cAMP-responsive element-binding protein-binding protein and steroid receptor coactivator-1a further enhanced the Fos/Jun-mediated transcription [2].
• Suppression of apoptosis by all-trans-retinoic acid. Dual intervention in the c-Jun n-terminal kinase-AP-1 pathway [22].
• These data elucidate, for the first time, that induction of MKP-1 by H(2)O(2) is mediated by the MAP kinase-AP-1 pathway and that the induced MKP-1 is involved in cellular defense against oxidative stress-induced apoptosis of mesangial cells [24].
• We conclude that in conscious rats, a moderate hypoxic stimulus elicits NMDA-dependent widespread mitogen-activated protein kinase activation in cortex, but selective SAPK/JNK-2 and AP-1 activation in the nucleus tractus solitarii, thereby suggesting a functional role for the SAPK/JNK-2-AP-1 pathway [5].
• The increase in transcription factor activator protein-1 (AP-1) DNA binding activity in response to Ang II was higher in rats fed the high-oil diet compared with those fed the standard diet (P < 0.001) [23].

Physical interactions of Jun

• Both NF-kappaB and AP-1 DNA were induced in HSC cultured in 3D collagen I gels and binding sites for these factors in the MMP-9 promoter were crucial for induction of transcription [25].
• The data seem to indicate that JNK and p38 MAPK activations are not necessarily coupled to DNA binding of AP-1, which can be either increased or inhibited when these kinases are activated [26].
• These results suggest a prominent role of JNK and p38, as well as their downstream AP-1 binding activation and p53 phosphorylation in mediating glutamate excitotoxicity [27].
• Delta9-tetrahydrocannabinol increases sequence-specific AP-1 DNA-binding activity and Fos-related antigens in the rat brain [28].
• Using electrophoretic mobility-shift assay and one-dimensional Western blot, we here report that delta9-THC increases Activator protein-1 (AP-1) DNA-binding and Fos-related antigen activity in discrete areas of the rat brain [28].

Regulatory relationships of Jun

• Recruitment of nuclear factor Y to the inverted CCAAT element (ICE) by c-Jun and E1A stimulates basal transcription of the bone sialoprotein gene in osteosarcoma cells [1].
• Apoptosis-signal regulating kinase-1 is involved in the low potassium-induced activation of p38 mitogen-activated protein kinase and c-Jun in cultured cerebellar granule neurons [4].
• The Ang II-induced activation of SP-1 and AP-1 were significantly suppressed by HS treatment [29].
• Heat shock treatment suppresses angiotensin II-induced SP-1 and AP-1 and stimulates Oct-1 DNA-binding activity in heart [29].
• Phorone, a glutathione (GSH) depletor, induces the expression of mRNAs of heme oxygenase-1 (HO-1) and c-jun by mediating the activation of activated protein-1 (AP-1) in rat livers [30].

Other interactions of Jun

• We next investigated which signaling pathway transduced by EGF was responsible for the Jun-induced synergism [31].
• The effects of c-Jun were abrogated by mutations in the ICE box and by co-expression of dominant negative nuclear factor Y, subunit A (NF-YA) [1].
• These results suggest that stathmin plays an essential role in anchorage-independent growth by cJun and may be a potential target for specific inhibitors for AP-1-dependent processes involved in carcinogenesis [32].
• These results demonstrate the differential engagement of MAPK signaling pathways following sensory stimulation and their relative effects upon AP-1 expression in the intact brain [33].
• Increase in messenger ribonucleic acid encoding the myometrial gap junction protein, connexin-43, requires protein synthesis and is associated with increased expression of the activator protein-1, c-fos [20].

Analytical, diagnostic and therapeutic context of Jun

• Using site-directed mutagenesis and EMSA techniques, we identified an activation protein 1 (AP1)-like element (-134/-128; TGAATCA) in the AVP gene 5'-promoter region, which is the sole responsible site for the Fos/Jun-mediated transcription [2].
• PPAR gamma:RXR activation also did not affect nuclear factor kappa B (NF-kappa B) nuclear translocation nor NF-kappa B and activator protein 1 (AP-1) activation in the electrophoretic mobility-shift assay [34].
• Involvement of ERKs in the induction and activation of AP-1 was also investigated using Northern blot analysis and a reporter assay [17].
• However, Western blots to c-Jun/AP1 (N) identified two bands [3].
• The mini-Fos (wbFos) and the mini-Jun (wbJun) proteins were purified to apparent homogeneity by using a nickel affinity chromatography procedure [35].

References