25:
123:) and "x" is any other amino acid; the spacing of these hydrophobic residues may be explained by examination of known structures that contain an NES, as the critical residues usually lie in the same face of adjacent secondary structures within a protein, which allows them to interact with the exportin.
289:
The binding of NES to the export receptor of a protein gives the universal export function of NES an individually specified activation of export to each protein. Studies of specified NES amino acid sequences for particular proteins show the possibility of blocking the NES activation of one protein
102:
NESs serve several vital cellular functions. They assist in regulating the position of proteins within the cell. Through this NESs affect transcription and several other nuclear functions that are essential to proper cell function. The export of many types of RNA from the nucleus is required for
228:
during cellular division. Due to the usually rapid proliferation of tumour cells, survivin is more expressed during the presence of cancer. The level of survivin correlates to how resistance to chemotherapy a cancerous cell is and how likely that cell is to replicate again. By producing
199:
the Ran-GTP to Ran-GDP, and this causes a shape change and subsequent exportin release. Once no longer bound to Ran, the exportin molecule loses affinity for the nuclear cargo as well, and the complex falls apart. Exportin and Ran-GDP are recycled to the nucleus separately, and
273:, which functions include cell motility and growth. The use of LBM as a NES inhibitor proved successful for actin resulting in accumulation of the protein within the nucleus, concluding universal functionality of NES throughout various protein functional groups.
127:(RNA) is composed of nucleotides, and thus, lacks the nuclear export signal to move out of the nucleus. As a result, most forms of RNA will bind to a protein molecule to form a ribonucleoprotein complex to be exported from the nucleus.
281:
Not all NES substrates are constitutively exported from the nucleus, meaning that CRM1-mediated export is a regulated event. Several ways of regulating NES-dependent export have been reported. These include masking/unmasking of NESs,
567:
Fukuda, Makoto; Asano, Shiro; Nakamura, Takahiro; Adachi, Makoto; Yoshida, Minoru; Yanagida, Mitsuhiro; Nishida, Eisuke (1997-11-20). "CRM1 is responsible for intracellular transport mediated by the nuclear export signal".
103:
proper cellular function. The NES determines what type of pathway the varying types of RNA may use to exit the nucleus and perform their function and the NESs may effect the directionality of molecules exiting the nucleus.
261:
has been identified as the export receptor for leucine-rich NESs in several organisms and is an evolutionarily conserved protein. The export mediated by CRM1 can be effectively inhibited by the fungicide
306:
Department of
Protein Chemistry. Every entry in its database includes information whether nuclear export signals were sufficient for export or if it was only mediated transport by CRM1 (exportin).
216:
drugs. By limiting a cell's nuclear export activity it may be possible to reverse this resistance. By inhibiting CRM1, the export receptor, export through the nuclear envelope may be slowed.
684:
Rowe, Thomas C.; Ostrov, David; Dawson, Jana L.; Pernazza, Danielle; Lawrence, Nicholas J.; Sullivan, Daniel M. (2013-11-15). "Targeting The
Nuclear Export Signal In Multiple Myeloma".
167:. In human language, this is an extension of the "common pattern" that includes hydrophilic residues surrounding it as well as slight variations in the length of
191:, increasing its affinity for the export cargo. Once the cargo is bound, the Ran-exportin-cargo complex moves out of the nucleus through the nuclear pore.
298:
NESbase is a database of proteins with experimentally verified leucine-rich nuclear export signals (NES). The verification is performed by, among others,
322:
Fukuda, Makoto; Asano, Shiro; Nakamura, Takahiro; Adachi, Makoto; Yoshida, Minoru; Yanagida, Mitsuhiro; Nishida, Eisuke (November 1997).
269:
Other proteins of various functions have also been experimentally inhibited of the NES signal such as the cyto-skeletal protein
629:"Nuclear export of actin: a novel mechanism regulating the subcellular localization of a major cytoskeletal protein"
770:
130:
299:
95:, which targets a protein located in the cytoplasm for import to the nucleus. The NES is recognized and bound by
246:
242:
799:
719:
Tanja la Cour; Ramneek Gupta; Kristoffer
Rapacki; Karen Skriver; Flemming M. Poulsen; Søren Brunak (2003).
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with an inhibitor for that amino acid sequence while other proteins of the same nucleus remain unaffected.
809:
92:
39:
192:
303:
250:
804:
201:
794:
133:
defines the NES motif for exportin within a single entry, TRG_NES_CRM1_1. The single-letter
577:
335:
8:
718:
134:
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339:
38:
Please expand the article to include this information. Further details may exist on the
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628:
609:
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324:"CRM1 is responsible for intracellular transport mediated by the nuclear export signal"
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Amino acid sequence causing a protein to be exported from the nucleus to the cytoplasm
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88:
36:
about non-CRM1 pathway (NESbase has a few unconventional ones but how do they work?).
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508:
El-Tanani, Mohamed; Dakir, El-Habib; Raynor, Bethany; Morgan, Richard (2016-03-14).
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Wada, Atsushi; Fukuda, Makoto; Mishima, Masanori; Nishida, Eisuke (1998-03-16).
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la Cour T, Kiemer L, Mølgaard A, Gupta R, Skriver K, Brunak S (June 2004).
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233:
to target the NES survivin, apoptosis of cancerous cells can be increased.
213:
84:
76:
670:
605:
387:"The nuclear export of circular RNAs is primarily defined by their length"
363:
736:
254:
112:
483:
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B (LMB), providing excellent experimental verification of this pathway.
510:"Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy"
323:
263:
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Computer analysis of known NESs found the most common spacing of the
80:
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The process of nuclear export is responsible for some resistance to
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217:
188:
96:
589:
347:
120:
72:
444:"Analysis and prediction of leucine-rich nuclear export signals"
24:
385:
Li, Zhengguo; Kearse, Michael G.; Huang, Chuan (2019-01-02).
270:
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and even disulfide bond formation as a result of oxidation.
721:"NESbase version 1.0: a database of nuclear export signals"
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183:
Nuclear export first begins with the binding of Ran-GTP (a
507:
441:
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321:
683:
626:
144:(.{0,1}.{2,3}{2,3}..{0,3})| (.{0,1}.{2,3}{2,3}..{0,3})
204:(GEF) in the nucleus switches the GDP for GTP on Ran.
786:
187:) to exportin. This causes a shape change in
384:
302:Center for Biological Sequence Analysis and
119:, where "L" is a hydrophobic residue (often
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660:
543:
525:
459:
418:
241:NES signals were first discovered in the
71:containing 4 hydrophobic residues in a
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151:are all hydrophobic residues, while
75:that targets it for export from the
18:
243:human immunodeficiency virus type 1
13:
91:. It has the opposite effect of a
14:
821:
764:
484:"ELM - Detail for TRG_NES_CRM1_1"
771:Eukaryotic Linear Motif resource
220:is a NES that inhibits cellular
131:Eukaryotic Linear Motif resource
23:
698:10.1182/blood.V122.21.1925.1925
300:Technical University of Denmark
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93:nuclear localization signal
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193:GTPase activating proteins
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147:In the above expression,
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304:University of Copenhagen
251:protein kinase inhibitor
245:(HIV-1) Rev protein and
224:. It interacts with the
645:10.1093/emboj/17.6.1635
202:guanine exchange factor
725:Nucleic Acids Research
527:10.3390/cancers8030035
461:10.1093/protein/gzh062
175:fragments seen above.
34:is missing information
448:Protein Eng. Des. Sel
61:nuclear export signal
800:Short linear motifs
582:1997Natur.390..308F
340:1997Natur.390..308F
137:pattern of NES, in
135:amino acid sequence
810:Molecular genetics
737:10.1093/nar/gkg101
139:regular expression
576:(6657): 308–311.
334:(6657): 308–311.
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195:(GAPs) then
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85:nuclear pore
83:through the
77:cell nucleus
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391:RNA Biology
255:karyopherin
253:(PKI). The
249:-dependent
113:hydrophobic
789:Categories
488:elm.eu.org
397:(1): 1–4.
310:References
277:Regulation
264:leptomycin
231:antibodies
117:LxxxLxxLxL
48:April 2019
706:0006-4971
653:0261-4189
598:0028-0836
536:2072-6694
520:(3): 35.
411:1547-6286
356:0028-0836
257:receptor
222:apoptosis
197:hydrolyze
185:G-protein
179:Mechanism
165:glutamine
107:Structure
97:exportins
81:cytoplasm
40:talk page
755:12520031
554:26985906
493:10 April
470:15314210
429:30526278
237:Examples
218:Survivin
189:exportin
780:NESbase
671:9501085
662:1170511
614:4420607
606:9384386
578:Bibcode
545:4810119
514:Cancers
420:6380329
372:4420607
364:9384386
336:Bibcode
294:NESbase
121:leucine
79:to the
73:protein
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570:Nature
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328:Nature
163:, and
686:Blood
610:S2CID
368:S2CID
271:actin
149:LIMVF
751:PMID
702:ISSN
667:PMID
649:ISSN
602:PMID
594:ISSN
550:PMID
532:ISSN
495:2019
466:PMID
425:PMID
407:ISSN
360:PMID
352:ISSN
259:CRM1
247:cAMP
171:and
741:PMC
733:doi
694:doi
690:122
657:PMC
641:doi
586:doi
574:390
540:PMC
522:doi
456:doi
415:PMC
399:doi
344:doi
332:390
169:xxx
153:DEQ
65:NES
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