Delayed response genes

Delayed response genes. These genes are induced by the activities of the transcription factors and other proteins produced or activated during the early response phase. Among the products of the delayed response genes are the Cdks, the cyclins, and other components required for cell division. 

Phosphorylation cascades are induced by both the activation of ras and increased levels of DAG and IP3 in the cell following EGF binding. One of the key enzymes activated in the phosphorylation cascade is MAPKK (mitogen activated protein kinase kinase). (A mitogen is any molecule that stimulates cell division). Activated MAPKK then phosphorylates both a tyrosine and a tryptophan of MAP kinase. (This unusual reaction appears to ensure that MAP kinase is activated only by MAPKK.) Active MAP kinase then phosphorylates a variety of cellular proteins. Among those are jun, fos, and myc. Phosphorylated jun and fos proteins then combine to form the transcription factor AP-1. AP-1 subsequently promotes the transcription of several delayed response genes. 

Because expression of delayed-response genes depends on proteins encoded by early-response genes, delayed-response genes are not transcribed when mitogens are added to Gq-arrested cells in the presence of an inhibitor of protein synthesis. Some delayed-response genes encode additional transcription factors (see below) others encode the D-type... 

Various polypeptide growth factors called mitogens stimulate cultured mammalian cells to proliferate by inducing expression of early-response genes. Many of these encode transcription factors that stimulate expression of delayed-response genes encoding the Gj CDKs, Gj cycllns, and E2F transcription factors. 

Tullai p)7, Schaffer ME, MuUenbrock S et al. Immediate-early and delayed primary response genes ate distinct in function and genomic architecture. J Biol Chem 2007 282(33) 23981-95... 

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All the anticancer drugs so far known are mutagenic. This means that they induce some mutations within the gene distributions on DNA, such mutations being responsible for delayed relapses in patients who were cured of their initial tumor. Thus, mutagenicity appears to be a very prejudicial side-effect for any therapeutical drug, at least when it reaches too a high level. 

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