Transcription regulation

Appetite-suppressing. Neuropqrtide modulators and gut hormones with anorexigenic effects are a-melanocortin-stimulating hormone (a-MSH), cocaine- and amphetamine-regulated transcript (CART), glucagon-like peptide-1 (GLP-1), leptin, insulin, oxyntomodulin, pancreatic peptide PP, peptide YY and PYY3 36, and others. 

CART (cocaine- and amphetamine-regulated transcript) is a hypothalamic peptide that inhibits both normal and starvation-induced feeding when injected into cerebral ventricles of rats. CART is co-localized with the anorexigenic peptide a-melanocyte-stimulating hormone in neurons of the arcuate nucleus. Secretion of CART is stimulated by leptin and CART may be an endogenous inhibitor of food intake. 

Cocaine- and amphetamine-regulated transcript (CART) peptides are putative neurotransmitters are found in those dopaminergic brain regions. Stimulants seem to alter CART mRNA and peptide levels [2]. 

Detailed analysis of the lambda repressor led to the important concept that transcription regulatory proteins have several functional domains. For example, lambda repressor binds to DNA with high affinity. Repressor monomers form dimers, dimers interact with each other, and repressor interacts with RNA polymerase. The protein-DNA interface and the three protein-protein interfaces all involve separate and distinct domains of the repressor molecule. As will be noted below (see Figure 39—17), this is a characteristic shared by most (perhaps all) molecules that regulate transcription. 

Figure 39-17. Proteins that regulate transcription have several domains. This hypothetical transcription factor has a DNA-binding domain (DBD) that is distinct from a ligand-binding domain (LBD) and several activation domains (ADs) (1-4). Other proteins may lack the DBD or LBD and all may have variable numbers of domains that contact other proteins, including co-regulators and those of the basal transcription complex (see also Chapters 42 and 43).

Figure 43-10. Regulation of the NF-kB pathway. NF-kB consists of two subunits, p50 and p65, which regulate transcription of many genes when in the nucleus. NF-kB Is restricted from entering the nucleus by IkB, an Inhibitor of NF-kB. IkB binds to—and masks—the nuclear localization signal of NF-kB.

A Large Number of Nuclear Receptor Coregulators Also Participate in Regulating Transcription... 

Kraus J, Bomer C, Giannini E, HoUt V (2003) The role of nuclear factor kappaB in tumor necrosis factor-regulated transcription of the human mu-opioid receptor gene. Mol Pharmacol 64 876-884 Law PY, Loh HH, Wei LN (2004) Insights into the receptor transcription and signaling implications in opioid tolerance and dependence. [Review] [123 refs]. Neuropharmacology 47(Suppl 1) 300-311... 

Kraus J, Bomer C, Giannini E, HoUt V (2003) The role of nuclear factor kappaB in tumor necrosis factor-regulated transcription of the human mu-opioid receptor gene. Mol Pharmacol 64 876-884... 

There are also monomeric G-proteins. Just like the trimeric G-pro-teins, they are involved as signal relays and timers. The Ras superfamily relays signals from receptor tyrosine kinases to downstream elements that eventually regulate transcription. Rho and Rac relay signals from cell-surface receptors to the cytoskeleton, while Rab regulates intracellular transport of vesicles. Regardless of what they do, they use the timer mechanism provided by the G-protein. Three-letter acronyms (TLA), such as Ras, Rho, and Rab, are difficult to remember, sometimes even when you know what the letters stand for. Unfortunately, there s nothing you can do about this except to memorize them. 

The cellular mechanism of action of hydrocortisone, a glucocorticoid, is also related to proteins but not by the enhancement of cAMP production. Hydrocortisone is transported by simple diffusion across the membrane of the cell into the cytoplasm and binds to a specific receptor The steroid-receptor complex is activated and enters the nucleus, where it regulates transcription of specific gene sequences into ribonucleic acid (RNA). Eventually, messenger RNA (mRNA) is translated to form specific proteins in the cytoplasm that are involved in the steroid-induced cellular response. 

Bayle, J.H. and Crabtree, G.R. 1997. Protein acetylation more than chromatin modification to regulate transcription. Chemistry and Biology 4(12), 885-888. 

Control of feeding behavior involves peripheral peptides (insulin, ghrelin, leptin) plus several peptides in the CNS (orexins/hypocretins, CCK, galanin, MSH, neuropeptide Y, CRH, cocaine-and-amphetamine-regulated transcript (CART)) [35, 36]. Some of the same peptides are involved in reward systems crucial to drug addiction. Specific receptor blockers are being tested for many of these peptide-receptor systems, with the hope of very selective actins with minimal side effects [35], For example, there are two CCK receptor subtypes, CCK-A and... 

Corticosteroid receptors regulate transcription in the nervous system 464... 

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