Proto-oncogenes functions

Roy LM, Haccard O, Izumi T, Lattes BG, Lewellyn AL, Mailer JL 1996 Mos proto-oncogene function during oocyte maturation in Xenopus. Oncogene 12 2203-2211 Sagata N 1997 What does Mos do in oocytes and somatic cells Bioessays 19 13-21... 

The relationship between the two receptors for NGF is complex and not yet completely understood. It has been suggested that the functional form of the NGF receptor is a heterodimer of p75 and pl40 proteins. BDNF and NT-3 bind to p75, but the functional receptors for these neurotrophins are the proto-oncogene products of and trkQ. 

Sagata, N., Oskarsson, M., Copeland, T Brumbaugh, J and Vande Woude, G. F. (1988). Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes. Nature 335 519-525. 

Winer, M. A., and Wolgemuth, D. J. (1993). Patterns of expression and potential functions of proto-oncogenes during mammalian spermatogenesis. In The Molecular Biology of the Male Reproductive System (De Kretser, D. M., ed.), pp. 143-179. Academic Press, San Diego. 

The c-mos proto-oncogene is unique in being specifically expressed in male and female germ cells, where it appears to play a central role in regulating the meiotic cell cycle. Its function is best understood in... 

The proteins encoded by most proto-oncogenes are normally expressed in a variety of differentiated cell types, where they generally function as... 

Paules, R. S., Buccione, R., Moschel, R. C., Vande Woude, G. F., and Eppig, J. J. (1989). Mouse mos proto-oncogene product is present and functions during oogenesis. Proc. Natl. Acad. Sci. USA 86 5395-5399. 

A unifying theme of the role of oncogene function in cell transformation is that the expression of the proto-oncogenes is normally tightly... 

Unlike tumor suppressors, in which loss-of-function mutations are required in both copies of the gene in a specific cell, a single gain-of-function mutation in a proto-oncogene is usually sufficient to give rise to cancer. 

Here are some insights into the functions of tumor suppressor genes and proto-oncogenes... 

The mutations that have converted the proto-oncogenes to their oncogene forms are gain-of-function or activating mutations. 

The activation of a proto-oncogene to an oncogene is based on mutations that can change the function and regulation of the affected protein by various mechanisms. Two pathways of activation can be roughly differentiated (Fig. 14.2). On the one hand, the structure of the coded protein may be affected on the other hand, activation may lead to a concentration increase in the protein. 

A frequent cause of activation of proto-oncogenes is a change in the structure of the coded protein, affecting the regulation and function. Via the oncogenic activation, there is no creation of completely new functions, but rather the normal function of a proto-oncogene product is modified and/or released from cellular regulation. 

Mutations may lead to loss of cellular control over the activity of a proto-oncogene. Frequently, this brings about constitutive activation of the signal protein. Thus, in the transforming v-raf gene, the N-terminal sequence section of Raf kinase is missing, on which both the autoinhibitory function and the phosphorylation sites of Raf kinase are locahzed (see 9.6). 

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