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Transcriptional Regulation of Ribonucleotide Reductase

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Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 309B)


The Swiss 3T3 cell system can be used to explore the molecular mechanism of proliferation. These fibroblasts can be arrested in a quiescent homogeneous Go/G1 state by serum deprivation and then induced to proliferate by a variety of mitogenic growth factors (1). An important endeavour in determining the basis of growth factor action is to elucidate the signal transduction pathways involved that result in the mitogenic response. These studies have led to the formulation of a model that proposes the existence of multiple growth factor-activated signalling pathways that synergistically lead to a mitogenic response (2). These pathways depicted in Figure 1 include one mediated by activation of protein kinase C, another mediated by cAMP-dependent protein kinase (A) and others that are, as yet, less clearly defined, which mediate responses to polypeptide growth factors that activate receptor tyrosine kinases (3). Activation of PKC specifically results in the rapid increase in the phosphorylation of an acidic cellular protein that migrates with an apparent Mr of 80000 (80K) (4). By contrast, the cAMP-mediated mitogenic response is characterised by the rapid increase in the phosphorylation of a Mr = 58000 cellular protein identified as vimentin (5). More distal effects include activation of the cellular proto-oncogenes c-fos and c-myc (6). Consistent with these physiologic events is the observation that these two genes have response elements in their 5′ upstream control elements that respond to either a PKC signal (AP-1 site) or a cAMP signal (CREB site). Even more distal events are under current investigation.

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© 1991 Plenum Press, New York

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Albert, D.A., Rozengurt, E. (1991). Transcriptional Regulation of Ribonucleotide Reductase. In: Harkness, R.A., Elion, G.B., Zöllner, N. (eds) Purine and Pyrimidine Metabolism in Man VII. Advances in Experimental Medicine and Biology, vol 309B. Springer, New York, NY.

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