Fos oncogene

Zhang, X. K., Wills, K. N., Husmann, M., Hermann, T, and Pfahl, M. (1991). Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities. Mol Cell Biol 11, 6016-6025. 

The leucine zipper motif (see Chapter 3) was first recognized in the amino acid sequences of a yeast transcription factor GCN4, the mammalian transcription factor C/EBP, and three oncogene products, Fos, Jun and Myc, which also act as transcription factors. When the sequences of these proteins are plotted on a helical wheel, a remarkable pattern of leucine residues... 

Gubits, R.M. Fairhurst, J.L. (1988). c-fos mRNA levels are increased by the cellular stressors, heat shock and sodium arsenite. Oncogene 3, 163-168. 

Basset-S6guin, N., Escot, C., Blanchard, J.M., Kerai, C., Verrier, B., Moin, H. and Guilhou, J.J. (1990). High levels of c-fos proto-oncogene expression in normal human adult skin. J. Invest. Dermatol. 94, 418-422. 

For example, c-Fos is heavily phosphorylated on a series of serine residues in the C-terminal domain of the protein by several types of protein kinases. The likely functional importance of these phosphorylation sites is indicated by the fact that the difference between c-Fos (the normal cellular form of the protein) and v-Fos (the viral oncogene product) is a frameshift mutation in the v-Fos protein, which obliterates the phosphorylated serine residues. It is speculated that the loss of these phosphorylation sites removes one mechanism by which the cell can regulate the protein, thereby leading to cellular transformation. 

Each cell of the human body carries the potential to become cancerous in the form of its proto-oncogenes. The case of the src gene is far from unique. A great many proto-oncogenes have been discovered some of the best known are myc, myb, ras, fes, fins, fos, and jun (these names derive from the retrovirus in which they were discovered e.g., ras comes from a rat sarcoma virus and fes from a feline sarcoma virus). It follows that each of our cells harbors a number of protooncogenes, each of which may become activated and contribute to the formation of a tumor. 

Finally, inappropriate expression of nuclear transcription factors can lead to cell transformation. For example, the products of he,fos and myc proto-oncogenes are transcription factors that regulate the expression of proteins that promote progression through the cell cycle. Levels of the Fos and Myc proteins are tightly regulated in normal cells. Uncontrolled expression of these proteins leads to cell proliferation. 

Remarkably, viral oncogene relatives are present in normal cells—these are termed proto-oncogenes. Therefore, each cell in the human body carries the potential to become cancerous in the form of its proto-oncogenes, which include myc, ms, myb, fes, fms, fos, and jun. 

DNA-binding proteins. A whole series of oncogenes code for transcription factors. Particularly important for cell proliferation are myc, as well as fos and jun. The protein products of the latter two genes form the transcription factor AP-1 as a heterodimer (see p. 244). 

Overexpression of one PKC isoenzyme may lead to altered expression and activity of one or more of the other PKC isoenzymes. For certain effects several PKC isoenzymes maybe involved. For example, the combined effects of PKCX, E and are essential for the transcriptional activation of c-fos by oncogenic H-ras (Kampfer et aL, 1998). PKCX. and participate in the ras-mediated reorganization of the F-actin cytoskeleton (Oberall et al., 1999). PKC can control the phosphorylation and activation of PKC5 (Ziegler et al., 1999). It may be that not the levels of PKCs, but the levels of the dephospho-rylated forms of PKCs are important for apoptosis (Whelan and Parker, 1998). 

A large number of proto-oncogenes code for transcription factors required for progression of the cell cycle and/or for the differentiation of the cell. The best known and investigated examples of oncogenic mutated transcription factors involve the jun, fos and myc genes and the genes for the T3 receptor and the vitamin A acid receptor. 

Transcription factors. The proto-oncogenes c-mt/c447 451a, c-myb,452 454 c-fos, c-jun and c-efs455 all encode nuclear proteins involved in regulation of transcription. The 39 kDa protein Jim, which is encoded by c-jun, is a major component of the transcriptional activator called AP-1.456 459 It binds to palindromic enhancer sites (Chapter 28) in DNA promoters to increase the transcription rate for a group of genes. 

Fos Protein encoded hy proto-oncogene/os PY Phosphotyrosine residue... 

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