Disease relevance of Fos

• To characterize the properties of these proteins, we have expressed polypeptides comprised of the dimerization and DNA-binding domains of Fos and Jun in Escherichia coli [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].
• Fibroblasts transformed by Fos oncogenes display increased expression of a number of genes implicated in tumor cell invasion and metastasis [3].
• Activation of c-fos, an immediate early gene, and the subsequent expression of the Fos protein have been noted following focal cerebral ischemia [4].
• This study aimed to examine the relationship between temporal and spatial expression patterns of Fos protein in the spinal dorsal horn neurons and thermal hyperalgesia behaviors in rats with chronic constriction injury (CCI) to the sciatic nerve [5].

Psychiatry related information on Fos

• Orexin and MCH neurons express c-Fos differently after sleep deprivation vs. recovery and bear different adrenergic receptors [6].
• The number of c-Fos-positive cells in the SON was significantly increased after 24 and 48 h of water deprivation [7].
• Following copulation, Fos was preferentially augmented in the caudal ventral medulla (CVM), a region mediating descending inhibition of penile reflexes, and which may be regulated by a forebrain circuit that includes the medial preoptic area (MPOA) [8].
• This study assessed the effects of subdiaphragmatic vagotomy in rats on fever, behavioural depression, as measured by the social interaction test, and Fos expression in the brain [9].
• Expression of Fos, Jun, and Krox family proteins in Alzheimer's disease [10].

High impact information on Fos

• TGF-beta 1 inhibition of transin/stromelysin gene expression is mediated through a Fos binding sequence [11].
• The Fos and Jun oncoproteins form dimeric complexes that stimulate transcription of genes containing activator protein-1 regulatory elements [12].
• Withdrawal, induced by the cannabinoid antagonist SR 141716A, was accompanied by a marked elevation in extracellular CRF concentration and a distinct pattern of Fos activation in the central nucleus of the amygdala [13].
• Regional brain activation was assessed by mapping of Fos-related protein expression in rats trained to self-administration of intravenous nicotine and cocaine [14].
• Light pulses also increased messenger RNA for the Fos protein and for the immediate-early protein NGFI-A in the rat SCN [15].

Chemical compound and disease context of Fos

• Tegaserod inhibits noxious rectal distention induced responses and limbic system c-Fos expression in rats with visceral hypersensitivity [16].
• After inhalation of 100% N2 (anoxia) or 8% CO2 (hypercapnia), neurons that express Fos protein (FOS) and/or Jun protein (JUN) were immunohistochemically identified in the CNS of rats anesthetized with urethane and alpha-chloralose [17].
• Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos expression after forepaw inflammation in infant rats [18].
• Six weeks after surgery, rats with aortic stenosis were randomized to receive either oral fosinopril 50 mg.kg-1.d-1 (Fos/LVH group, n = 38) or no drug (LVH group, n = 36) for 15 weeks [19].
• Neonatal capsaicin treatment attenuates spinal Fos activation and dynorphin gene expression following peripheral tissue inflammation and hyperalgesia [20].

Biological context of Fos

• AP-1 is an ubiquitous transcription factor which is composed of the Jun and Fos proto-oncogene proteins and is thought to play a role in both cell proliferation and differentiation [21].
• 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 [22].
• Thus, potentially, these different states of Fos and Jun can be recognized and regulated independently by phosphorylation [23].
• PP2B independent dephosphorylation contributes to degradation of c-Fos protein during oxidative stress response of cardiomyocytes [24].
• With high percentage gel electrophoresis, multiple c-Fos bands were resolved by Western blot analyses, indicating post-translational modification of newly synthesized c-Fos protein after H2O2 exposure [24].

Anatomical context of Fos

• The expression of c-Fos and c-Myc increased at 2 h after exposure in neurons of the cerebral cortex, thalamus, and hippocampus, and this c-Fos immunoreactivity remained elevated for the entire observation period [25].
• Increased Fos Immunoreactivity in Suprachiasmatic Nucleus before Luteinizing Hormone Surge in Estrogen-Treated Ovariectomized Female Rats [26].
• GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata after chronic colonic inflammation in rats [27].
• In contrast to normal 208F rat fibroblasts, Fos-transformed 208F fibroblasts are growth factor independent for invasion [3].
• In cells primed to grow, blocking c-Fos expression determined neurite retraction [28].

Associations of Fos 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].
• On the other hand, in EB rats there were significant peaks of LH levels and Fos levels in GnRH neurons and the AVPV between ZT11-12 and ZT13-14 [26].
• DNA binding of the Fos-Jun heterodimer was modulated by reduction-oxidation (redox) of a single conserved cysteine residue in the DNA-binding domains of the two proteins [29].
• These patterns of NGFI-A activation are remarkably similar to those found for Fos-like immunoreactivity following acute amphetamine and cocaine treatments, suggesting that coordinate activation of members of at least two immediate-early gene families occurs in the striatum following catecholaminergic stimulation [30].
• Oxidants cause activation of the AP-1 transcription factor in cardiomyocytes. c-Fos, a component of the AP-1 transcription factor, is transiently induced by H2O2 and the induction is sensitive to the protein synthesis inhibitor cycloheximide [24].

Physical interactions of Fos

• We have also found that heterodimer formation of Maf-2 with c-Fos dramatically changes the specificity of DNA binding and trans-activation activity from that of the Maf-2 homodimer [31].
• DNase I footprinting experiments demonstrated that Jun homodimeric complexes and Fos-Jun heterodimeric complexes interacted with the same site on the human metallothionein IIA gene [1].

Co-localisations of Fos

• Another subpopulation comprised larger neurons that exhibited intense neurotensin immunoreactivity in perikarya and proximal processes that was rarely co-localized with Fos immunoreactivity [32].

Regulatory relationships of Fos

• Estradiol treatment increases CCK-induced c-Fos expression in the brains of ovariectomized rats [33].
• The COX-2 inhibitor blocked LPS-induced fever and Fos expression in sites such as the ventromedial preoptic nucleus (VMPO) and the hypothalamic paraventricular nucleus (PVH), although Fos-immunoreactivity in the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), and parabrachial nucleus (PB) remained [34].
• Third, we found that most Kiss1 neurons in the AVPV coexpress the immediate early gene Fos coincidently with the LH surge, but virtually none coexpressed Fos on diestrus [35].
• Intracerebroventricular injection (ICV) of NMU induced the expression of Fos protein in the SCN cells and caused a phase-dependent phase shift of the circadian locomotor activity rhythm [36].
• The neuronal marker protein gene product 9.5 and the glial markers S-100 and glial fibrillary acidic proteins showed that RX-77368 induced Fos in both myenteric neurons and glia [37].

Other interactions of Fos

• In vasopressinergic neurons, the expression of the Fos/Jun family proteins is known to be rapidly induced after these stimuli as well [2].
• Here, rat brains were investigated immunohistochemically for the expression of c-Fos, c-Myc, and beta-APP during the first 3 weeks postexposure to impulse noise of 198 or 202 dB [25].
• Maf-2 heterodimerizes with c-Fos [31].
• These data indicate that the transcription factors c-Fos and c-Jun are important in the regulation of Cx43 expression [38].
• Here we used c-Fos immunohistochemistry to determine whether estradiol increases CCK-induced neuronal activation in several brain regions implicated in the control of feeding [33].

Analytical, diagnostic and therapeutic context of Fos

• The mini-Fos (wbFos) and the mini-Jun (wbJun) proteins were purified to apparent homogeneity by using a nickel affinity chromatography procedure [1].
• 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].
• Immunohistochemical analyses for Fos and GnRH and enzyme-linked immunosorbent assays for LH were then performed [26].
• Treatment of immunoprecipitated c-Fos protein with the type 2 serine/threonine phosphatase A (PP2A) and immunoblotting of c-Fos protein with antibodies against phosphorylated serine or threonine demonstrated that c-Fos was phosphorylated at serine residues [24].
• Combined retrograde Fluorogold (FG) labeling and c-Fos immunocytochemistry showed that throughout the CN about 60% (2270/3652) of the c-Fos-IR cells contained FG, confirming that they were cuneothalamic projection neurons (CTNs) [39].

References