Nuclear translocation of transcription factors

MTF-1 has recently been linked to the transcriptional regulation of the y-glutamyl cysteine synthetase gene which encodes an enzyme needed for GSH synthesis [45], strengthening the role of this transcription factor in oxidative stress which, depending on the stimulus, can lead to GSH depletion. Since heme-hemopexin increases oxi- 

Taken together these data from our most recent studies with heme-hemopexin connect the increased cellular oxidation state and production of cuprous ions at cell surface with nuclear translocation of MTF-1 and MT-1 transcriptional regulation by hemopexin. 

5 Role of redox-active metals in the regulation of the metallothionein 

Isabel Moura, Helder Lopes, Cristina Costa, J. J. G. Moura and Graham W Pettigrew 

---

Hsieh TC, Lu X, Wang Z, Wu JM. 2006. Induction of quinone reductase NQOl by resveratrol in human K562 cells involves the antioxidant response element ARE and is accompanied by nuclear translocation of transcription factor Nrf2. Med Chem 2 275-285. 

The failure of antioxidant mechanisms to correct redox disequilibrium could lead to the escalation of oxidative to tier 2. Tier 2 cellular responses are characterized by the activation of cellular signaling pathway such as stress-activated kinases (p38 MAP kinase and JNK) along with activation and nuclear translocation of transcription factors NF-kB and STAT-1. NF-KB-induced transcriptional activation leads to the production of a number of pro-inflammatory cytokines, including the neutrophil chemoattractant IL-8. STAT-1 activation stimulates the increased production of CXC-motif chemokines that function in lymphocyte recruitment and activation. Therefore, tier 2 oxidative responses result in an inflammatory response in the lung. 

Lin, Y. Z., Yao, S. Y., Veach, R. A., Torgerson, T. R., and Hawiger, J. (1995) Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J. Biol. Chem. 270, 14,255-14,258. 

A cytotoxic activity and the ability to induce nuclear translocation of transcription factor NF-kB were identified as important cellular reactions when cells are stimulated by Maillard reaction mixtures or food items such as coffee, which are rich in Maillard products Both cellular effects, however, were fully or at least partially abolished, when coffee extracts or Maillard reaction mixtures were administered to the cells together with catalase. These results indicate that Maillard reaction products are able to generate H2O2, which then induces cellular reactions, such as cell death or immunomodulation. 

Fig. 1 Localization of TLRs in immune cells, their ligands and a representation of TLR signaling pathways. Nucleic acid-recognizing TLRs 3, 7, 8, and 9 are located in the endolysosomes. Signaling by these receptors upon activation by their respective ligands leads to the activation and nuclear translocation of transcription factors such as the IRFs, NF-kB, and API, which promote expression of cytokines...

The expression of genes involved in cell proliferation and cell death is regulated by nuclear transcriptional factors. NFAT (Nuclear Factor of Activated T cells) proteins are a family of Ca2+-dependent transcription factors (Crabtree, 2001), whose nuclear translocation and transcriptional activity is regulated by Ca2+/calmodulin-dependent protein phosphatase, calcineurin (Crabtree, 2001). Thus, NFAT proteins can potentially be activated by diverse stimuli that lead to increased intracellular calcium levels. The NF-kB (nuclear factor kappa B) family... 

Abbott BD, Probst MR. 1995. Developmental expression of two members of a new class of transcription factors II. Expression of aryl hydrocarbon receptor nuclear translocator in the C57BL/6N mouse embryo. Develop Dynam 204 144-155... 

Rummel C, Hubschle T, Gerstberger R, Roth J (2004) Nuclear translocation of the transcription factor STAT3 in the guinea pig brain during systemic or localized inflammation. J Physiol... 

Figure 16.2. Signaling for memory formation. Short-term memory formation involves the activation of PKA, but no gene transcription. Activation of G-protein coupled receptors by excitatory stimuli activates adenylyl cyclase. This leads to the elevation of cAMP level, which subsequently activates PKA. Activated PKA undertakes modulation of channels thereby enhancing conductivity. However, prolonged/ repeated activation of this system results in nuclear translocation of PKA, which is the central molecular basis of long-term memory formation. Activated PKA and MAPK activate transcription factor CREB-1 while suppressing the inhibitory CREB-2. Activated CREB-1 binds to CRE region in promoters of early genes like C/EBP. Interestingly, C/EBP itself is a transcription factor that subsequently teams up with CREB to express late memory genes.

The activation and proliferation of T lymphocytes are considered to be the basic cellular immune responses leading ultimately to rejection of transplanted tissue in the absence of effective immunosuppression. An important effect of T cell activation is production of the Ca VcalmoduHn-activated form of the serine/threonine phosphatase calcineurin. The latter is responsible for the activation and nuclear translocation of a number of transcription factors, such as nuclear factor of activated T (NFAT) cells. 

---