Translocator complexes

Fig. 2.2 Simplified scheme of oxidant/antioxidant regulation ofNF-KB activation. Different stimuli, leading to an increase of ROS generation inside the ceU, activate the phosphorylation of IkB inhibitory protein and the subsequent proteolysis. Thioredoxin (Trx) may reduce activated NF-kB proteins facilitating nuclear translocation.Qnce released from IkB, the NF-kB complex translocates into the nucleus and the binding to DNA domain in the promoters and enhancers of genes such as TNF-a, IL-1, proliferation and chemotactic factors, adhesion molecule. Some of these genes, in turn, may further induce NF-kB activation, leading to a vicious circle if the regulatory cellular system escapes from...

The three activated STATs disengage from the receptor and bind to the cytoplasmic protein, p48. This entire complex translocates to the nucleus, where it interacts directly with upstream regulatory regions of IFN-sensitive genes. These nucleotide sequences are termed interferon-stimulated response elements (ISREs). This induces/augments expression of specific genes, as discussed later. 

All corticosteroids have the same general mechanism of action they traverse cell membranes and bind to a specific cytoplasmic receptor. The steroid-receptor complex translocates to the cell nucleus, where it attaches to nuclear binding sites and initiates synthesis of messenger ribonucleic acid (mRNA). The novel proteins that are formed may exert a variety of effects on cellular functions. The precise mechanisms whereby the corticosteroids exert their therapeutic benefit in asthma remain unclear, although the benefit is likely to be due to several actions rather than one specific action and is related to their ability to inhibit inflammatory processes. At the molecular level, corticosteroids regulate the transcription of a number of genes, including those for several cytokines. 

Betamethasone is a corticosteroid. Corticosteroids are very lipophilic (due to their hydrocarbon skeleton) and as a result can passively diffuse into target cells. It acts by binding to the intracellular corticosteroid receptor protein, which is found within the cytosol. The resulting complex translocates to the nucleus and induces synthesis of mediator proteins (e.g. metabolic enzymes and lipocortin). The binding of steroid hormones to their receptors causes changes in gene transcription and cell function. Corticosteroids reduce the inflammatory reaction by limiting capillary dilatation and vascular permeability. 

Inv l4(qli q32). or complex translocations involving both chromosomes 14 Unknown T-PLL Aggressive 75... 

Although Fig. 15 only shows reactions at the Q site, a complete Q-cycle requires the oxidation of two QH2 molecules in two successive series of turnovers. As Fig. 15 (d) shows, the electron on Cyt / (LP) moves up to Cyt / (HP). This electron from the / -heme chain is used to reduce an oxidized quinone bound at the Qf (or Qj) site. Thus the two catalytic sites in Cyt b are involved in the oxidation or reduction of quinone. The integration of the oxidation and reduciton reactions with the release or uptake of protons in the aqueous phases results in the complex translocating protons across the membrane and generating a proton gradient, as already discussed in Section UFA. and Fig. 11. 

Fig. 5.n Activation of the MAPK cascade via/ -arrestin and C protein-coupled receptors. A complex is formed between / -arrestin and the various components of a MAPK module (see Chapter 10) in the cytosol. This multiprotein complex translocates to the plasma membrane bound receptor following ligand binding. / -arrestin functions as a scaffold for the MAPK module and promotes internalization of the whole complex. This leads to generation of active MAPK and stimulation of transcription. MAPK mitogen activated protein kinase, MEK MAPK/ERK kinase, MEKK MEK kinase. 

The mode of action of Smad 4 clearly differs from that of the other members of the Smad family. Smad 4 binds to phosphorylated R-Smads and forms trimeric complexes composed of two R-Smad molecules and one Smad 4 molecule. These complexes translocate to the nucleus, where they bind to related DNA elements and activate the transcription of target genes. The mechanism of transcription regulation by Smads is complex and includes both positive and negative influences. Generally, Smad-dependent regulation of transcription requires the interaction with other transcription factors, such as members of the FoxH 1 family of forkhead transcription factors, the Vitamin D receptor and the c-Jun transcription factor, among others (review Attisano et al., 2001). Futhermore, Smads can interact with coactivators and corepressors of transcription and thereby recruit, e. g., histone acetylase activity or histone deacetylase activity to chromatin. 

After the entire complex translocates Into the nucleus, Ran-GTP causes dissociation of Imp-p as discussed In Chapter 12. 

After phosphorylated R-Smad binds a co-Smad, the resulting complex translocates Into the nucleus, where it interacts with various transcription factors to Induce expression of target genes (see Figure 14-2). 

MS ]" are the concentrations of carrier ion complex on the left and right sides of the membrane and F is the Faraday. The complex translocation rate constants depend on voltage approximately as... 

McKinney, C D, Golden, W. L., Gemma, N W, Swerdlow, S H, and Williams, M. E. (1994) RARA and PML gene rearrangements in acute promyelocytic leukaemia with complex translocations and atypical features Genes, Chromosomes Cancer 9,49-56... 

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