Jun oncogene

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... 

Benhar, M. et al., Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress, Mol. Cell. Biol., 21, 6913, 2001. 

Sevilla A, Santos CR, Barcia R, Vega FM, Lazo PA (2004a) c-Jun phosphorylation by the human vaccinia-related kinase 1 (VRKl) and its cooperation with the N-terminal kinase of c-Jun (JNK). Oncogene 23(55) 8950-8958... 

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. 

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. 

Deoxycholic acid has also been demonstrated to activate other pivotal oncogenic pathways in CRC cells in vitro including p-catenin/T-cell factor-mediated transcription, extra-cellular signal-regulated kinase activation downstream of the epidermal growth factor receptor and Jun-N-terminal kinase... 

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). 

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. 

Fig. 3. A simplified illustration of BCR-ABL and SRC family kinase involvement in oncogenic signaling pathways. The inhibitory effect is indicated by the upside-down T s. ABL = Abelson tyrosine kinase BCR = breakpoint cluster region FAK = focal adhesion kinase Grb-2 = growth factor receptor-bound protein 2 HcK = hematopoietic cell kinase JNK = Jun amino-terminal kinase P = phosphate group PI3 K = phosphatidylinositol-3-kinase SFK = SRC family kinases StatS = signal transducer and activator of transcription 5. (Reprinted with permission from Ref (123)). 

Hydrogen peroxide transformed mouse myeloid progenitor cells (FDC-Pl) from interleukin-3 dependence to factor independence, but only at cytotoxic concentrations (> 12/5 pmol/L). Such a transformation was not induced by non-specific insults to the cells, such as sodium fluoride or heat shock treatment. The transformed cells produced tumours when injected into pre-irradiated mice (Crawford Greenberger, 1991). Hydrogen peroxide (10 pmol/L) induced overexpression of the proto-oncogene c-jun in hamster tracheal epithelial (HTE) cells c-jun overexpression led to proliferation and increased growth rate, as well as increased anchorage-independence of HTE cells (Timblin et al., 1995). 

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. 

Jun Protein encoded by proto-oncogene RTK Receptor tyrosine kinase... 

The myc Gene Product The jun and fos Gene Products The Transition from Protooncogene to Oncogene Carcinogenesis Is a Multistep Process... 

The oncogene of the FBJ murine osteosarcoma virus (fos) codes for a related nuclear protein that participates in transcriptional regulation. In human fibroblasts the fos protein is mostly associated with c-jun. The fos-jun complex binds specifically to DNA. Since fos alone does not show specific DNA binding, it is believed that jun is responsible for this affinity. Although jun can form homodimers that bind to DNA, the heterodimers formed between fos and jun show a greater affinity. The heterodimers are also more effective in transcription activation therefore the heterodimer is probably the functionally relevant state of the jun and fos proteins. 

Morgan JI, Curran T. Stimulus-transcription coupling in the nervous system involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci 1991 14 421-451. 

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