NESbase version 1.0: a database of nuclear export signals

Cour, Tanja la; Gupta, Ramneek; Rapacki, Kristoffer; Skriver, Karen; Poulsen, Flemming M.; Brunak, Søren

doi:10.1093/nar/gkg101

Cited by 204 publications

(187 citation statements)

References 26 publications

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“…Consistently, a similar C-terminus portion of MondoA, a WBSCR14 paralog, recently was shown to include a cytoplasmic localization domain (7,23,32). Between residues 81 and 146, the sequence 86 LTHLFECLSL 95 conforms to the NES signature (L-x(2,3) (33). To confirm that this stretch of residues was participating in the active nuclear export of Wbscr14-z, we engineered a double mutant by changing two of the characteristic NES signature residues.…”

Section: Mapping Of the Wbscr14 Nes Activitymentioning

confidence: 79%

The subcellular localization of the ChoRE-binding protein, encoded by the Williams–Beuren syndrome critical region gene 14, is regulated by 14-3-3

Merla

Howald

Antonarakis

et al. 2004

Human Molecular Genetics

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Section: Mapping Of the Wbscr14 Nes Activitymentioning

confidence: 79%

The subcellular localization of the ChoRE-binding protein, encoded by the Williams–Beuren syndrome critical region gene 14, is regulated by 14-3-3

Merla

Howald

Antonarakis

et al. 2004

Human Molecular Genetics

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“…Many NES sequences have been characterized as having regularly spaced leucine or hydrophobic residues, similar to that of the Rev protein from human immunodeficiency virus type 1 (HIV-1). However, export signals often do not conform to the Rev paradigm and must be identified by experimental approaches (11).…”

Section: Subcellular Distribution Of Nipah Virus N-terminal Fragmentsmentioning

confidence: 99%

Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion

Rodriguez

Cruz

Horvath

2004

J Virol

124

123

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The V proteins of Nipah virus and Hendra virus have been demonstrated to bind to cellular STAT1 and STAT2 proteins to form high-molecular-weight complexes that inhibit interferon (IFN)-induced antiviral transcription by preventing STAT nuclear accumulation. Analysis of the Nipah virus V protein has revealed a region between amino acids 174 and 192 that functions as a CRM1-dependent nuclear export signal (NES).This peptide is sufficient to complement an export-defective human immunodeficiency virus Rev protein, and deletion and substitution mutagenesis revealed that this peptide is necessary for both V protein shuttling and cytoplasmic retention of STAT1 and STAT2 proteins. However, the NES is not required for V-dependent IFN signaling inhibition. IFN signaling is blocked primarily by interaction between Nipah virus V residues 100 to 160 and STAT1 residues 509 to 712. Interaction with STAT2 requires a larger Nipah virus V segment between amino acids 100 and 300, but deletion of residues 230 to 237 greatly reduced STAT2 coprecipitation. Further, V protein interactions with cellular STAT1 is a prerequisite for STAT2 binding, and sequential immunoprecipitations demonstrate that V, STAT1, and STAT2 can form a tripartite complex. These findings characterize essential regions for Henipavirus V proteins that represent potential targets for therapeutic intervention.The biological effects of alpha and beta interferon (IFN-␣ and -␤) are mediated by a transcription factor complex, ISGF3, that is comprised of the signal transducer and activator of transcription (STAT) proteins, STAT1 and STAT2, in association with a DNA-binding subunit, an IFN regulatory factor, IRF9 (1, 12). IFN-induced, ISGF3-mediated transcription results in a cellular antiviral state that provides protection against a broad range of virus types. In response to this negative selection, most viruses have evolved adaptations that allow them to evade IFN-induced innate antiviral responses (13,26).In the case of the paramyxovirus family of negative-strand RNA viruses, IFN signaling to ISGF3 is disrupted by direct targeting of STAT proteins (4). Current evidence from the study of several family members indicates that the common outcome of STAT targeting and IFN evasion is achieved by individual paramyxovirus species through a diverse range of molecular mechanisms. For example, the Rubulaviruses, simian virus 5 (SV5), human parainfluenza virus 2, and mumps virus all encode STAT-directed E3 ubiquitin ligase activities that function in combination with cellular proteins to target STAT1, STAT2, or STAT3 for proteasomal degradation (5,18,19,28,29). Distinctly, measles virus, a prototype Morbillivirus, does not induce STAT ubiquitylation and degradation but instead prevents IFN-induced ISGF3 assembly and STAT protein nuclear translocation (17, 27). These IFN evasion mechanisms rely on protein-protein interactions between STATs and the paramyxovirus-encoded V protein. The paramyxovirus V protein is characterized by a highly conserved cysteine-rich C-terminal domain (...

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“…Mutations of leucines in the NES disrupt the ability of the protein to localize in the cytoplasm. At least 75 proteins containing a NES have been identified to date (la Cour et al, 2003). These include cellular proteins, many of which are involved in transcription, cell signaling cascades, oncogenic transformation and regulation of the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

Involvement of protein phosphatase 2A nuclear accumulation and subsequent inactivation of activator protein-1 in leptomycin B-inhibited cyclin D1 expression

et al. 2006

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Leptomycin B (LMB) is a Streptomyces metabolite that causes the specific inhibition of the nuclear export of proteins containing a nuclear export signal (NES). LMB was reported to inhibit cell cycle progression in fission yeast and mammalian cells, however, the mechanism underlying LMB-induced cell cycle arrest is still obscure. In this study, we found that in serum-starved NIH3T3 cells, LMB inhibited serum-induced cyclin D1 expression at the level of transcription. However, this inhibition was reversed by inhibitors of protein phosphatase 2A (PP2A). Furthermore, we found that PP2A accumulated in the nucleus upon treatment with LMB. The finding prompted us to identify the functional NES in PP2A catalytic subunit a. These results indicated that LMB inhibited the chromosomal region maintenance 1 (CRM1)-dependent nuclear export of PP2A, resulting in sustained dephosphorylation in the nucleus. Although phosphorylation of c-Jun at Ser-63 is required for activator protein 1 (AP-1)-dependent expression of cyclin D1, it decreased in LMBtreated cells compared to untreated cells. Moreover, the inhibitors of PP2A restored the levels of c-Jun phosphorylated at Ser-63. We propose that inhibition of cyclin D1 expression by LMB is mediated by the LMB-induced nuclear accumulation of PP2A, leading to sustained dephosphorylation of c-Jun at Ser-63, which leads to inactivation of the transcription of the AP-1-responsive cyclin D1 gene.

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NESbase version 1.0: a database of nuclear export signals

Cited by 204 publications

References 26 publications

The subcellular localization of the ChoRE-binding protein, encoded by the Williams–Beuren syndrome critical region gene 14, is regulated by 14-3-3

The subcellular localization of the ChoRE-binding protein, encoded by the Williams–Beuren syndrome critical region gene 14, is regulated by 14-3-3

Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion

Involvement of protein phosphatase 2A nuclear accumulation and subsequent inactivation of activator protein-1 in leptomycin B-inhibited cyclin D1 expression

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