Transcription and Translation

Na+/Ca2+ Exchangers. Figure 3 Potential steps in the pharmacological regulation of NCX isoform expression and activity. This scheme reproduces the potential levels at which drugs can interfere with the transduction, transcription, translation, and activity of NCX. 

Both the heat and cold shock response are universal and have been studied extensively. The major heat shock proteins (HSPs) are highly conserved. They are involved in the homeostatic adaptation of cells to harsh environmental conditions. Some act as molecular chaperones for protein folding, while others are involved in the processing of denatured polypeptides whose accumulation would be deleterious. The cold shock results in the transient induction of cold shock proteins (CSPs), which include a family of small acidic proteins carrying the cold shock domain. The CSPs appear to be involved in various cellular functions such as transcription, translation and DNA recombination. 

Many mechanisms have been found to contribute to desensitization. Operating at transcriptional, translational, and protein levels, some mechanisms function relatively slowly—over the course of hours or days. Other mechanisms of desensitization occur quickly, within minutes. Rapid modulation of receptor function in desensitized cells may involve critical covalent modification of the receptor, especially by phosphorylation on specific amino acid residues, association of these receptors with other proteins, or changes in their subcellular location. 

The oxidative phosphorylation system contains over 80 polypeptides. Only 13 of them are encoded by mtDNA, which is contained within mitochondria, and all the other proteins that reside in the mitochondrion are nuclear gene products. Mitochondria depend on nuclear genes for the synthesis and assembly of the enzymes for mtDNA replication, transcription, translation, and repair (Tl). The proteins involved in heme synthesis, substrate oxidation by TCA cycle, degradation of fatty acids by /i-oxidalion, part of the urea cycle, and regulation of apoptosis that occurs in mitochondria are all made by the genes in nuclear DNA. 

T1. Taanman, J. W., The mitochondrial genome Structure, transcription, translation and replication. Biochim. Biophys. Acta 1410, 103-123 (1999). 

The levels of particular enzymes (and indeed of specific proteins in general) is determined by the balance of protein degradation versus the specific expression of the protein (through the process of specific gene transcription, translation and post-translational processing of the protein). Genes can either be constitutively expressed (in which case they are normally always being transcribed) or are inducible, that is, specific transcription factors are activated... 

COX-2 and iNOS. Some steroid hormone receptors complexed with their specific hormone ligand act as DNA-binding transactivators to switch on transcription of particular genes. However, in the hormone-free state these proteins can act as repressors and block initiation of transcription of these genes. DNA and associated transcription, translation and replication processes are similar in plants and non-plant eukaryotes. Nevertheless, some plants elaborate DNA binding compounds or compounds that otherwise interfere with gene expression and DNA replication (Tables 9.1—9.4). 

Galdzicki Z, Siarey RJ (2003) Understanding mental retardation in Down s syndrome using trisomy 16 mouse models. Genes Brain Behav 2 167-178 Garber K, Smith KT, Reines D, Warren ST (2006) Transcription, translation and fragile X syndrome. Curr Opin Genet Dev 16 270-275... 

Holstein, S.A., Wohlford-Lenane, C.L., and Hohl, R.J. (2002). Conseqnences of mevalonate depletion. Differential transcriptional, translational, and post-translational up-regulation of Ras, Rapla, RhoA, and RhoB. / Bio/ Chem 277 10678-10682. 

The regulation of the synthesis of the polypeptides of PS II appears to be particularly complex, with evidence for regulation at transcriptional, translational and post-translational levels. The synthesis of the individual polypeptides does not appear to be tightly coordinated, with certain polypeptides accumulating in the absence of other PS II polypeptides under a variety of experimental conditions. The synthesis of a functional PS II complex is strongly dependent on light, both for its effect on the transcription of PS II genes and for its absolute requirement for Chi synthesis. 

The synthesis of the polypeptides of the core complex takes place exclusively in the chloroplasts, as indicated by synthesis in isolated chloroplasts or by translation of chloroplast RNA in vitro. Regulation of the synthesis appears to operate at transcriptional, translational and post-translational levels, with light playing a major role. 

In this chapter we have considered drugs which act on transcription, translation, and replication by acting directly on DNA and RNA. There are other drugs (e.g. nalidixic acid) which affect these processes, but since these drugs work by inhibiting enzymes rather than by a direct interaction with DNA or RNA, they have not been mentioned here. 

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