Nuclear export signal

Expoitins are transport receptors at the nuclear pore complex needed for the selective export of proteins from the nucleus into the cytoplasm. They recognize nuclear export signal sequences of cargo proteins. 

Proteins similar to importins, referred to as ex-portins, are involved in export of many macromolecules from the nucleus. Cargo molecules for export carry nuclear export signals (NESs). Ran proteins are involved in this process also, and it is now established that the processes of import and export share a number of common feamres. 

Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM (1999) A leucine-rich nuclear export signal in the p53 tetramerization domain regulation of subcellular localization and p53 activity by NES masking. EMBO J 18 1660-1672... 

Li W, Yu SW, Kong AN. 2006. Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain. J Biol Chem 281 27251-27263. 

Li W, Jain MR, Chen C, Yue X, Hebbar Y, Zhou R, Kong AN. 2005. Nrf2 Possesses a redox-insensitive nuclear export signal overlapping with the leucine zipper motif. J Biol Chem 280 28430-28438. 

Fischer, U., Huber, J., Boelens, W.C., Mattaj, I.W. and Luhrmann, R. (1995) The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Cell, 82, 475 183. 

Bogerd, H.P., Fridell, R.A., Benson, R.E. and Cullen, B.R. (1996) Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by an in vivo randomization-selection assay. Mol. Cell. Biol., 16, 4207-A214. 

Fomerod, M., Ohno, M., Yoshida, M. and Mattaj, I.W. (1997) CRM1 is an export receptor for leucine-rich nuclear export signals. Cell, 90, 1051-1060. 

Murphy, R. and Wente, S.R. (1996) An RNA-export mediator with an essential nuclear export signal. Nature, 383, 357-360. 

Pasquinelli, A.E., Powers, M.A., Lund, E., Forbes, D. and Dahlberg, J.E. (1997b) Inhibition of mRNA export in vertebrate cells by nuclear export signals conjugates. Proc. Natl Acad. Sci. USA, 94, 14394-14399. 

Eberhart DE, Malter HE, Feng Y, et al. The fragile X mental retardation protein is a ribonucleopro-tein containing both nuclear localization and nuclear export signals. Hum Mol Genet 5 1083-1091,1996. 

Long-term potentiation Nuclear export signal... 

Huang IT, Miyamoto S (2001) Postrepression activation of NF-kappaB requires the amino-terminal nuclear export signal specific to IkappaBalpha. Mol Cell Biol 21 4737-4747 Huang CJ, Nazarian R, Lee J, Zhao PM, Espinosa-Jeffrey A et al (2002) Tumor necrosis factor modulates transcription of myelin basic protein gene through nuclear factor kappa B in a human oligodendroglioma ceU line. Int J Dev Neurosd 20 289-296... 

Fig. 10.8 Above, import of the transcription factor NF-AT4 into the nucleus. In activated cells, import is initiated by calcineurin-mediated dephosphorylation of NF-AT4. Dephosphorylation unmasks the nuclear-localization signal (NLS), and at the same time blocks the nuclear export signal (NES). The NES is recognized by the exportin protein (Crml). Nuclear export is an active process. Moreover, nuclear export requires rephosphorylation of the NF-AT4 transcription factor. It is indicated that dephosphorylation by calcineurin and nuclear export are mutually exclusive, because calcineurin and Crm 1 compete for a common binding site on NES. When NES binds to Crml, NT-AT4 is exported from the nucleus, and when calcineurin binds to NES, NF-AT4 remains in the nucleus and forms a transcriptionally active complex. Below, how the extent of dephosphorylation controls the transcriptional activity of NF-AT4. When NF-AT4 is fully phosphorylated, NLS is hidden and the transcription factor remains in the cytoplasm. When NF-AT4 is only partially dephosphorylated, NLS is exposed and can interact with importin a/b which promote nuclear import, and at the same time, NES can interact with the exportin Crml, which promotes nuclear export. The consequence is that the transcription factor shuttles between the nucleus and the cytoplasm and is not transcriptionally active. In order to become transcriptionally fully active, NF-AT4 must be completely dephosphorylated. This prevents export from the nucleus by blocking NES, and may increase the affinity of the transcription factor for DNA by exposure of its trans-activating domain (TAD). (The entire scheme is reproduced with permission of Drs Patrick G. Hogan and Anjana Rao and Nature from Fig. 1 in ref. 68.)...

Arabidopsis clock proteins LHY and CCAl (Schaffer et al. 1998 Wang and Tobin 1998). LCLl contains a nuclear localization signal (NLS) as well as a nuclear export signal (NES) and is therefore an actively translocating nucleo-cytoplasmic shuttle protein. As a control experiment, we monitored the intracellular dynamics of the small protein pa-GFP alone. In contrast to LCLl, the distribution of pa-GFP from the nucleus to the cytoplasm happens by diffusion, only. 

Schmied, K. and Merkle, T. (2006) The Arabidopsis LHY/CCAl-like (LCL) protein family MYB transcription factors containing a nuclear export signal are co-regulators of the circadian clock, submitted. 

Fukuda, M., Asano, S., Nakamura, T et al. (1997). CRMl is responsible for intracellular transport mediated by the nuclear export signal. Nature, 390, 308-311. 

Kndo, N., Taoka, H., Toda, T., Yoshida, M., Horinonchi, S. (1999). A novel nuclear export signal sensitive to oxidative stress in the fission yeast transcription factor Papl. 

Ngnyen, A. N., Ikner, A. D., Shiozaki, M., Warren, S. M., Shiozaki, K. (2002). Cytoplasmic localization of Wisl MAPKK by nuclear export signal is important for nnclear targeting of Spcl/Styl MARK in fission yeast. Mol. Biol. Cell, 13, 2651-2663. 

Callystatin A (4) is a higly potent cytotoxic polyketide isolated from Callyspongia truncata Its absolute structure was determined by chemical method and confirmed by total synthesis. Its potent cytotoxicity (IC50 = 0.022 nmol against human pharyngeal carcinoma KB cells) was presumed to be due to the inhibition of nuclear export signal (NES)-dependent export of nuclear proteins. ... 

Exportins Transport Proteins Containing Nuclear-Export Signals out of the Nucleus... 

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