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Section: Genetics » Genetics of Cancer : Proto-oncogenes, Oncogenes and Tumour Suppressor Genes
 
 
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  Cellular functions of oncoproteins
 
     
 
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Genetics of Cancer : Proto-oncogenes, Oncogenes and Tumour Suppressor Genes
Viral oncogenes (y-onc genes)
Isolated oncogenes for transfection assay
Activation of proto-oncogenes by mutation
Activation of proto-oncogenes by insertions, translocations and amplification
Tumour suppressor genes or anti-oncogenes
Cellular functions of oncoproteins
Regulation of gene expression by oncoproteins
Signal transduction by oncoproteins (G proteins)


Cellular Functions of Oncoproteins
Oncoproteins and their corresponding proto-oricoproteins are variously distributed in the nucleus, cytoplasm and the nuclear membrane. On the cell or nuclear membrane, they may be found on the cytoplasmic face or may be found as transmembrane proteins. Distribution of a number of oncoproteins is shown in Figure 48.8. They are also classified, on the basis of function into following four groups : (i) tyrosine kinases (subdivided into cytoplasmic proteins and membrane-bound growth factor receptors), (ii) growth factors, (iii) GTP-binding proteins and (iv) nuclear proteins.

Src (associated with RSV) was the first oncoprotein of the kinase type, that was characterized. Src is located on the cytoplasmic face of the cell membrane (Fig. 45.8). In the cells transformed by RSV, phosphotyrosine is increased ten times, and Src is responsible not only for its own phosphorylation (at residues 416, 527) but also for phosphorylation of tyrosine in several other proteins. Its catalytic activity resides in the c-terminal half of the protein and this activity in v-Src is 20 times that in c-Src. The oncogenic property of Src also depends on the replacement of N-terminal amino acid of Src by an unusual amino acid 'myristic acid', a phenomenon described as myristylation. How does phosphorylation of c-Src and v-Src regulates cellular function is being studied in some detail.
 
Location of oncoproteins—transmembrane proteins, membrane associated proteins, cytoplasmic proteins and nuclear proteins.
Fig. 45.8. Location of oncoproteins—transmembrane proteins, membrane associated proteins, cytoplasmic proteins and nuclear proteins.

There are also proto-oncogenes, which code for receptors, residing as trans-membrane domains. A model for the function of these receptors assumes that binding of a ligand to the extracellular domain activates the tyrosine kinase activity of the intracellular domain, which leads to phosphorylation of cellular substrates. The best examples are EGF (epidermal growth factor) receptor coded by c-erbB, and CSF-1 (colony stimulating factor) coded by c-fms.

There are also oncoproteins like pDGF (platelet derived growth factor), which stimulates the expression of several genes, including c-myc and c-fos.

 
     






     
     
 
 
     
 
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