Gene-activation signals

TABLE 4.2. Gene-activation signals and tissue or cell sources that enhance isolation and identification of target genes in eukaryotes... 

As with signal transduction and second messenger systems, the mechanism of gene activation allows for amplification of the hormone s effect. 

The signal crosses the membrane and activates gene transcription. Signals for soluble receptors include steroid hormones, retinoic acid, thyroid hormone, and vitamin D. 

Hoffmann, A., Levchenko, A., Scott, M. L and Baltimore, D. (2002) The IkappaB-NF-KappaB signaling module temporal control and selective gene activation. Science 298, 1241-1245. 

Fig. 13.3 HIF-la and p53 as mediators of RNI signaling. RNI affect HIF-la stabilization to promote its interaction with HIF-ip. Recruitment ofthe coactivator p300/CBP causes gene activation to elicit pathophysiological responses. RNI activate...

J. Dubrulle, M. J. McGrew, and O. Pourquie, FGF signaling controls somite boundary position and regulates segmentation clock control of spatiotemporal Hox gene activation. Cell 106,219— 232 (2001). 

As described later, hemopexin interacts with a variety of heme analogs, two of which, Sn-protoporphyrin IX (SnPP) and Co-protoporphyrin IX (CoPP), helped clarify the mechanism of MT-1 gene regulation by hemopexin. SnPP-hemopexin interacts with the hemopexin receptor and the SnPP (an inhibitor of HO-1, (91)) enters the cell and induces HO-1 (92). In contrast, CoPP-hemopexin interacts with the receptor, but CoPP is not internalized. Interestingly, the mere occupancy of the receptor by hemopexin is sufficient to activate signaling pathways and consequent induction of MT-1 (90, 92, 93), whereas heme uptake is required for activation of HO-1 gene transcription (92, 93). 

The hemopexin heme transport system thus acts as an early warning system for cells by activating signaling pathways (including the N-terminal c-Jun kinase, kinases to release RbIA/NFkB family members for nuclear translocation) and transcription of the HO-1 and MT-1 genes. The details of this aspect of hemopexin function with redox-active copper as an initial event in the coordinated induction of HO-1 and MT-1 by heme-hemopexin have recently been reviewed (89) and are not presented in detail here. 

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