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c-fos

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Phylogeny of c-fos

C-fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos, according

to molecular biology and genetics. It was discovered as the transforming gene of the FBJ MSV

in rat fibroblasts first. Immunohistochemical techniques can identify the protein product, c-fos

protein. As a result, c-fos expression could be used as a marker for neuronal activity throughout

the neuraxis following peripheral stimulation (Jahnson et al 2019). The c-fos proto-oncogenes

encode proteins that form a complex that regulates transcription from AP-1 activation elements

in promoters. It shares homology with c-putative Jun's DNA binding domain.

Organisms where c-fos are found

Experiments involving counting of labelled cells was done in the hypothalamus, spinal cord and

thalamus and there was little c fos discovered in animals. However prolonged inhalation of

anesthesia induced the number of cells labelled at brain sites. The data done on The ventrolateral

medulla, the posterior hypothalamic nucleus, and the reuniens and paraventricular thalamic

nuclei which are all parts of the brain suggested that c fos can act as transsynaptic marker in

neurons.

Functional/structural role of c-fos

Although c-Fos and other IEGs eventually function as transcription factors and regulate

downstream target genes, c-Fos has been most widely used as a functional marker of activity in

neurons and neuronal circuitries in response to a variety of stimuli. It is used as a neuronal

activity marker and has been linked to a variety of neural and behavioral responses to acute

stimuli expression (Rodriguez & Caputto, 2019). It also participates in critical cellular events

such as cell proliferation, differentiation, and survival, as well as genes associated with hypoxia
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and angiogenesis, making its dysregulation an important factor in cancer development. The

structural role of c fos is that in Its protein product, c-Fos, is a short-lived transcription factor that

heterodimerizes with other proteins in the AP-1 transcription complex via leucine zipper/leucine

zipper interactions to bind to specific DNA sequences. The proteasome degrades it almost

entirely, if not entirely.

Cells and tissues that express c-Fos in organisms

C fos Is found little in animal cells but prolonged inhalation of anesthesia increase the number of

cells in brain. It is found in Schwann cells, precursor cells, eucaryotic cell, Jurkat cells, murine

cells as well as in the asynchronous cells. The connective osteoid and brain tissues also you can

find the c fos.

Unique structural components of c-Fos

The fos oncogene's unique association with bone tumors drew attention to it at first and this

makes it unique. It has 380 amino acids and has a region called leucine zipper which is

responsible for dimerization and binding of DNA as well as acts as a transactivation domain at c

terminus. It can also form homodimers.

Role of c-Fos in the aspect of metabolism

C fos role a s a functional marker and transcription factor in activation of neurons has been used

since it was discovered more years ago. It is an inducible gene that is encoded in transcription

factor or in third messenger which takes part in stimulus transcription in coupling and mediation

of extracellular signals in long term changes in cellular phenotype. C fos has been a powerful

tool used in delineating individual neurons and also extending circuitries responsible for external

stimuli (Ying et al 2020). There are still questions about how widespread c-fos induction is in
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central neurons and whether the threshold of c-fos induction is comparable along a specific

neuronal pathway. The limitation of this technology is that c-fos does not identify cells with a net

inhibitory synaptic or transcriptional drive, and c-fos induction, as a generic marker of trans-

synaptic activation, does not provide evidence for transcriptional activation of specific target

genes in a particular cell type of interest.

Role of c-Fos in interactions with other molecules

The interactions of c fos with c Jun/AP 1 is described in form of an experiment that was done as

is leads to promotion of AP 1 responsive genes transcription. In this experiment the ability of the

c-fos gene product, Fos, to act as a transcriptional trans-activator was investigated using MT-fos

chimeric genes. Induction of Fos expression in 3T3MTfos cells resulted in specific trans-

activation of an AP-1 responsive reporter gene. However, induction of Fos expression in

F9MTfos cells did not result in trans-activation. Because F9 cells, unlike NIH3T3 cells, do not

contain detectable levels of AP-1, we investigated whether a Math Eq expression vector can

restore c Fos's transactivating effect in F9MTfos cells. The specific trans-activating effect of c

Fos on AP-1 responsive constructs was restored after transfection with a functional Math Eq

vector. Anti-c Fos antisera precipitated a protein complex composed of c Fos and several c Fos

associated proteins when incubated with nondenatured cell extracts (FAP). FAP is one of these.

The findings suggest that c Fos is a trans-acting factor capable of stimulating gene expression

via interaction with the sequence-specific transcription factor AP-1 rather than direct binding to

DNA. As a result, AP-1 recognition of specific cis-elements is required for Fos-mediated gene

expression stimulation.
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Experimental findings of c-Fos molecule

The technology used was the immunohistochemical techniques in finding the c fos in the

brainstem neuronal populations which is involved in ventilatory adaption in hypercapnia or

hypoxia. Two methods for identifying involved neuronal populations in animals were described,

one in vivo and one ex vivo in deafferented brainstem preparations. Animals were subjected to

hypercapnic or hypoxic gas mixtures in the laboratory. Deafferent preparations were super fused

with hypoxic or hypercapnic artificial cerebrospinal fluid ex vivo. Under normoxic and

normocapnic conditions, either control in vivo animals or ex vivo preparations were maintained.

The comparison of these two approaches enables the determination of the origin of neuronal

activation. Brainstems were collected, fixed, and cut into sections both in vivo and ex vivo. After

preparing the sections, immunohistochemical detection of the c-FOS protein was performed to

identify the brainstem groups of cells activated by hypoxic or hypercapnic stimulations. In

brainstem respiratory structures, labeled cells were counted. In comparison to the control

condition, hypoxia or hypercapnia increased the number of c-FOS labeled cells in several

specific brainstem sites, forming part of the neuronal pathways involved in the adaptation of the

central respiratory drive.

Conclusion

c-Fos is a 380 amino acid protein with a basic leucine zipper region for dimerization and DNA

binding and a transactivation domain at the C-terminus, and it can form homodimers like Jun

proteins. Quaternary structures is that it depends on the conformational of monomers and not 1,

and C/Ebp which are zinc finger, c finger, basic finger respectively. Knowing the refractory
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period is better as it explains the evolutionary adaptations of c fos in that there have been reports

that the biochemical differences in the discrete in the neuronal systems between rodents and

primates or humans and non-humans primates that they contain cortical synapse which are

connections of the striatal dopami9nergic systems (Vu et al 2021). Based on the role of c-fos in

adipocyte differentiation, our discovery of a mutation that initiates a repression mechanism at the

c-fos promoter supports the hypothesis that decreased c-fos expression may contribute to CGL

by interfering with adipocyte development. The full-length Co-c-Fos cDNA sequence is made up

of a 1290 bp coding sequence that encodes 429 amino acids. It was discovered in rat fibroblasts

as the transforming gene of the FBJ MSV (Wiedmann et al 2021). Few animals contain c fos. It

is a small protein as it contains only 380 amino acids. C fos is essential as it is necessary for

HGF mediated gene regulation and cell migration Schwann cells.

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References

Janson, N. D., Jehanathan, N., Jung, S., Priyathilaka, T. T., Nam, B. H., Kim, M. J., & Lee, J.

(2019). Insight into the molecular function and transcriptional regulation of activator

protein 1 (AP-1) components c-Jun/c-Fos ortholog in red lip mullet (Liza

haematocheila). Fish & Shellfish Immunology, 93, 597-611.

Rodríguez-Berdini, L., & Caputto, B. L. (2019). Lipid metabolism in neurons: a brief story of a

novel c-Fos-dependent mechanism for the regulation of their synthesis. Frontiers in

Cellular Neuroscience, 13, 198.

Ying, C. A. I., Zheng, K., Li, R. B., Yu, S. Y., Ning, L. I. U., Ji, J. J., ... & XU, X. Y. (2020).

Proteomics Study on the Differentially Expressed Proteins in c-fos-silenced Cells

Exposed to PM2. 5. Biomedical and Environmental Sciences, 33(9), 680-689.

Vu, T. O., Tran, P. T., Seo, W., Lee, J. H., Min, B. S., & Kim, J. A. (2021). Flavonoids from the

peels of Citrus unshiu Markov. and their inhibitory effects on RANKL-induced

osteoclastogenesis through the downregulation of c-Fos signaling in vitro. Bioorganic

Chemistry, 107, 104613.

Wiedmann, N. M., Wong, A. W., Keast, J. R., & Osborne, P. B. (2021). Sex differences in c‐Fos

and EGR‐1/Zif268 activity maps of rat sacral spinal cord following cystometry‐induced

micturition. Journal of Comparative Neurology, 529(2), 311-326.

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