Regulation of Expression

OATP expression is controlled by similar nuclear factors to NTCP but, unlike NTCP, the activity is down-regulated by phosphorylation of serine 

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NOS (eNOS, NOS IH, NOS3). Classically, nNOS and eNOS were considered constitutive enzymes, whereas iNOS is cytokine-induced. Recent evidence suggests that nNOS and eNOS are also subject to important regulation of expression [1 ]. Within the human species, amino acid sequences of the three NOS isoforms share 52-58% identity. Each isoform is well conserved across mammalian species (>90% amino acid identity for nNOS and eNOS, >80% for iNOS). NOS enzymes exist in organisms as low as nematodes, protozoa, and even in plants (Fig. 1). 

Dingledine, R et al. (1999) The glutamate receptor ion channels. Pharmacol. Rev. 51 7-61. Frerking, M and Nicoll, RA (2000) Synaptic kainate receptors. Curr. Opin. Neurobiol. 10 342-351. Gegelashvili, G and Schousboe, A (1997) High affinity glutamate transporters regulation of expression and activity. Mol. Pharmacol. 52 6-15. 

The expansion of our knowledge of the structure and function of Na,K-ATPase is reflected in a rapid succession of reviews on Na,K-ATPase genes and regulation of expression [17], subunit assembly and functional maturation [20], the isozymes of Na,K-ATPase [18], and the stability of a subunit isoforms during evolution [21], physiological aspects and regulation of Na,K-ATPase [22], reconstitution and cation exchange [23], chemical modification [24], and occlusion of cations [25]. Other valuable sources are the review articles [26] and recent developments [27] reported at the International Na,K-pump Conference in September 1990. 

Douglass, J.O. Civelli, 0. Birnberg, N. Comb, M. Uhler, M. Lissitzky, J.C. and Herbert, E. Regulation of expression of opioid peptide genes. Ann Neurol 16(Supp1) S22-S30, 1984. 

Migeotte I, Franssen J-D, Goriely S, Willems F, Parmentier M. Distribution and regulation of expression of the putative human chemokine receptor HCR in leukocyte populations. Eur J Immunol 2002 32 494-501. 

Taylor P, Li Y, Camp S, et al. 1993. Structure and regulation of expression of the acetylcholinesterase gene. Chem Biol Interactions 87 199-207. 

Regulation of expression levels of the genes transferred has proven problematic. 

Fig. 3. Schematic representation of a signaling pathway for the 5-HT2A receptor, in which activation by 5-HT leads to the regulation of expression of an immediate early gene, Zif268.

Regulation of expression may occur at both the transcriptional and post-transcriptional levels. The mRNA for GM-CSF contains (in common with those of some other cytokines) conserved regulatory sequences in the 3 untranslated region, which may affect its rate of translation. The gene is constitutively transcribed in monocytes, endothelial cells and fibroblasts, but the mRNA is unstable and so does not accumulate to levels sufficient to allow translation into significant amounts of protein. Activation of these cells results in the increased expression of GM-CSF protein, which arises from both an enhanced rate of transcription (as detected in nuclear runoff experiments) and also an increased stability of the mRNA, perhaps by mechanisms analogous to those described above during activation of G-CSF expression ( 2.2.3.1). 

The regulation of expression of receptors on the plasma membrane is thus controlled by several factors ... 

Baum LO, Strobel HW. 1997. Regulation of expression of cytochrome P-450 2D mRNA in rat brain with steroid hormones. Brain Res 765 67-73. 

Immediately after a report confirmed that the promoter for SEPSl was stimulated by proinflammatory cytokines, and also showed that this promoter was the target of the critical inflammatory regulator NF-kB. The data included direct binding of this transcription factor to the promoter region using gel mobility shift assays. However, the stimulation of the promoter by cytokines and activation of NF-kB did not result in synergistic production of the mRNA. The role that the cytokines or inflammation plays in regulation of expression of selenoprotein S is not yet clear. 

Holyoake TL, Jiang X, Jorgensen HG et al. Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor independent growth in vitro in association with up-regulation of expression of interleukin 3. Blood 2001 97 720 728. 

Blobe GC, Sachs CW, Khan WA, Fabbro D, Stabel S, Wetsel WC, Obeid LM, Fine RL, Hannun YA (1993) Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional significance of enhanced expression of PKCa. J Biol Chem 268 658-664... 

Novak, R.F. and Woodcroft, K.J. (2000) The alcohol-inducible form of cytochrome P450 (CYP 2E1) role in toxicology and regulation of expression. Arch. Pharmaceutical Research, 23, 267-282. 

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