Cytoplasmic inhibitor protein

In an other hand, NO inhibits iNOS expression. When NO provokes the p53 accumulation, this one could in return inhibit iNOS gene transcription [154], Repression is observed in DLD-1 cells (human colon carcinoma) or Calu 6 cells (human pulmonary carcinoma) which express wild type p53. High NO concentration leads to p53 nitrosylation and inhibits the repression [114]. The wild type but not the mutated or the nitrosylated protein binds the iNOS gene promoter. Moreover, exogeneous NO produced by NO donors can inhibit NFkB activity in whole cells and in acellular preparation [155-157]. Those results have been confirmed in endothelial cells in which NO produced by eNOS inhibits NFkB activity and iNOS gene transcription [158], The inhibition can be explain in parts by NFkB sub-unit p50 nitrosylation [155], but also by its cytoplasmic inhibitor protein IxBa stabilisation (IkB proteins functionally retain NF-... 

A specific protein inhibitor for 5 -nucleotidase has been purified from E. coli cell cytoplasm (10, 16). It prevents the action of the enzyme on 5 -AMP, ATP, and UDPG. It also inhibits the hydrolysis of 5 -AMP by the 5 -nucleotidases from A. aerogenes, S. sonnei, and S. typhimurium (10). Other Enterobacteriaceae also possess similar intracellular protein inhibitors (18) which inhibit all hydrolytic activities of the 5 -nucleo-tidase of these organisms. The relevance of this inhibitor protein to the action of the enzyme in vivo is not known. 

Steroid hormone receptors are homodimeric nuclear receptors. In the absence of hormone, they are trapped in the cytoplasm by inhibitor proteins. When bound to their ligands, they can translocate to the nucleus and activate transcription of target genes (see Figure 11-44). 

Fig. 15. Intracellular processes of activation of NFkB. The NFkB is present in latent form in the cytoplasm as a result of binding to the inhibitor protein IkB. Cytokine-induced signal transduction results in selective IkB phosphorylation, which is in turn ubiquitinated and degraded by the protea-some pathway. Free NFkB migrates to the mucleus by several localization signals. Binding of NFkB to its specific site of genes induces transcription of several NFKB-dependent genes. NFkB is then inactivated by newly synthesized IkB both in the cytoplasm and nucleus.

NF-kB comprises a family of inducible transcription factors that serve as relevant mediators of the inflammatory response. This factor is also involved in protecting cells from undergoing apoptosis in response to DNA damage or treatment with cytokine [89]. Normally, NF-kB is kept inactive by a cytoplasmic inhibitor of kB (IkB) proteins, which are phosphorylated by a cellular kinase complex known as IKK, made up of two kinases, IKK-a and IKK-p. The phosphorylation of IkB by these kinases leads to the degradation of the proteins and to the translocation of NF-kB to the nucleus. Once in the nucleus, NF-kB activates gene expression of cells exposed to growth factors and cytokines [90,91]. Activation of the NF-kB pathway is thus involved in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis and asthma... 

FIGURE 10.8 A schematic diagram of the Na, K -ATPase in mammalian plasma membrane. ATP hydrolysis occurs on the cytoplasmic side of the membrane, Na ions are transported out of the cell, and ions are transported in. The transport stoichiometry is 3 Na out and 2 in per ATP hydrolyzed. The specific inhibitor ouabain (Figure 7.12) and other cardiac glycosides inhibit Na, K -ATPase by binding on the extracellular surface of the pump protein. 

In addition to effects on biochemical reactions, the inhibitors may influence the permeability of the various cellular membranes and through physical and chemical effects may alter the structure of other subcellular structures such as proteins, nucleic acid, and spindle fibers. Unfortunately, few definite examples can be listed. The action of colchicine and podophyllin in interfering with cell division is well known. The effect of various lactones (coumarin, parasorbic acid, and protoanemonin) on mitotic activity was discussed above. Disturbances to cytoplasmic and vacuolar structure, and the morphology of mitochondria imposed by protoanemonin, were also mentioned. Interference with protein configuration and loss of biological activity was attributed to incorporation of azetidine-2-carboxylic acid into mung bean protein in place of proline. 

Hyperphosphorylation of ERAK-1 by itself and ERAK-4 causes ERAK-1 to dissociate from the membrane-bound complex. Tumour necrosis factor (TNF) receptor-associated factor-6 ( TRAF-6), a cytoplasmic protein, is activated by ERAK-1 and with TAB-2, another cytoplasmic protein, activates transforming growth factor-P (TFG-P)-activating kinase (TAK-1). During this process both TRAF-6 and TAK-1 become ubiquitinated. TAK-1 then promotes activation of the IkB kinases, or the IKK family, EKKa and EKK 3 (found in a complex with NFicB-essential modulator [NEMO]), which phosphorylate the IkB family, notably IkB-u. IkB-u is an inhibitor of NFkB as it sequesters NFkB in an... 

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