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Characterization of Diverse Functions of NRF1 Nuclear Localization Sequence.

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Τίτλος: Characterization of Diverse Functions of NRF1 Nuclear Localization Sequence.
Συγγραφείς: Shamrin G; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Electronic address: shamringleb@gmail.com., Kajla G; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan., Kumar S; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan., Liu YN; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Electronic address: liuy@tmu.edu.tw., Chen HY; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Electronic address: hyichen@tmu.edu.tw.
Πηγή: Journal of molecular biology [J Mol Biol] 2026 Oct 01; Vol. 438 (19), pp. 169920. Date of Electronic Publication: 2026 Jul 03.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Elsevier
Original Publication: 1959- : London : Academic Press
Ιατρικοί όροι (MeSH): Nuclear Localization Signals*/metabolism , Nuclear Localization Signals*/genetics , Nuclear Respiratory Factor 1*/metabolism , Nuclear Respiratory Factor 1*/genetics , Nuclear Respiratory Factor 1*/chemistry, Cell Nucleus/metabolism ; Humans ; Active Transport, Cell Nucleus ; Animals ; Phosphorylation ; Transcriptional Activation ; Amino Acid Sequence
Περίληψη: Most of the transcription factors require a nuclear localization signal (NLS) to translocate to the nucleus via the nuclear import machinery. Initially, classical monopartite NLS with an arginine-lysine basic box was discovered, later less common bipartite NLS with two basic boxes separated with a spacer was found in certain nuclear proteins. Although both types of signals perform the same nuclear translocation function, it is not clear what role does the spacer play in the translocation and what benefits do two basic boxes give to a protein. We studied NRF1 - a transcription factor with a bipartite NLS. We dissected the function of the NLS of NRF1 and found that the spacer plays an auxiliary role in the transcriptional activity of NRF1, and phosphorylation inside the spacer regulates the nuclear translocation of NRF1 when combined with the posttranslational modifications of the NLS. We discovered that the spacer of NRF1 is not necessary for the translocation but it is indispensable for the transcriptional activation. We found that only a single basic box at the N-terminal of NLS is necessary for the nuclear translocation, while C-terminal basic box deletion shows no effect on the NRF1 subcellular localization. Additionally, we found a new downstream target of NRF1-ZNF777.
(Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: localization; nucleus; promoter; transcription; translocation
Substance Nomenclature: 0 (Nuclear Localization Signals)
0 (Nuclear Respiratory Factor 1)
Entry Date(s): Date Created: 20260703 Date Completed: 20260806 Latest Revision: 20260806
Update Code: 20260807
DOI: 10.1016/j.jmb.2026.169920
PMID: 42398803
Βάση Δεδομένων: MEDLINE
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  Data: Characterization of Diverse Functions of NRF1 Nuclear Localization Sequence.
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  Data: <searchLink fieldCode="AU" term="%22Shamrin+G%22">Shamrin G</searchLink>; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Electronic address: shamringleb@gmail.com.<br /><searchLink fieldCode="AU" term="%22Kajla+G%22">Kajla G</searchLink>; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.<br /><searchLink fieldCode="AU" term="%22Kumar+S%22">Kumar S</searchLink>; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.<br /><searchLink fieldCode="AU" term="%22Liu+YN%22">Liu YN</searchLink>; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Electronic address: liuy@tmu.edu.tw.<br /><searchLink fieldCode="AU" term="%22Chen+HY%22">Chen HY</searchLink>; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Electronic address: hyichen@tmu.edu.tw.
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  Data: <searchLink fieldCode="JN" term="%222985088R%22">Journal of molecular biology</searchLink> [J Mol Biol] 2026 Oct 01; Vol. 438 (19), pp. 169920. <i>Date of Electronic Publication: </i>2026 Jul 03.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Elsevier%22">Elsevier </searchLink><i>Country of Publication: </i>Netherlands <i>NLM ID: </i>2985088R <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1089-8638 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2200222836%22">00222836 </searchLink><i>NLM ISO Abbreviation: </i>J Mol Biol <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: Amsterdam : Elsevier<br /><i>Original Publication</i>: 1959- : London : Academic Press
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  Data: <searchLink fieldCode="MM" term="%22Nuclear+Localization+Signals%22">Nuclear Localization Signals*</searchLink>/<searchLink fieldCode="MM" term="%22Nuclear+Localization+Signals+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Nuclear+Localization+Signals%22">Nuclear Localization Signals*</searchLink>/<searchLink fieldCode="MM" term="%22Nuclear+Localization+Signals+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Nuclear+Respiratory+Factor+1%22">Nuclear Respiratory Factor 1*</searchLink>/<searchLink fieldCode="MM" term="%22Nuclear+Respiratory+Factor+1+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Nuclear+Respiratory+Factor+1%22">Nuclear Respiratory Factor 1*</searchLink>/<searchLink fieldCode="MM" term="%22Nuclear+Respiratory+Factor+1+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Nuclear+Respiratory+Factor+1%22">Nuclear Respiratory Factor 1*</searchLink>/<searchLink fieldCode="MM" term="%22Nuclear+Respiratory+Factor+1+chemistry%22">chemistry</searchLink><br /><searchLink fieldCode="MH" term="%22Cell+Nucleus%22">Cell Nucleus</searchLink>/<searchLink fieldCode="MH" term="%22Cell+Nucleus+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Active+Transport%2C+Cell+Nucleus%22">Active Transport, Cell Nucleus</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Phosphorylation%22">Phosphorylation</searchLink> ; <searchLink fieldCode="MH" term="%22Transcriptional+Activation%22">Transcriptional Activation</searchLink> ; <searchLink fieldCode="MH" term="%22Amino+Acid+Sequence%22">Amino Acid Sequence</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Most of the transcription factors require a nuclear localization signal (NLS) to translocate to the nucleus via the nuclear import machinery. Initially, classical monopartite NLS with an arginine-lysine basic box was discovered, later less common bipartite NLS with two basic boxes separated with a spacer was found in certain nuclear proteins. Although both types of signals perform the same nuclear translocation function, it is not clear what role does the spacer play in the translocation and what benefits do two basic boxes give to a protein. We studied NRF1 - a transcription factor with a bipartite NLS. We dissected the function of the NLS of NRF1 and found that the spacer plays an auxiliary role in the transcriptional activity of NRF1, and phosphorylation inside the spacer regulates the nuclear translocation of NRF1 when combined with the posttranslational modifications of the NLS. We discovered that the spacer of NRF1 is not necessary for the translocation but it is indispensable for the transcriptional activation. We found that only a single basic box at the N-terminal of NLS is necessary for the nuclear translocation, while C-terminal basic box deletion shows no effect on the NRF1 subcellular localization. Additionally, we found a new downstream target of NRF1-ZNF777.<br /> (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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  Group:
  Data: <i>Keywords: </i>localization; nucleus; promoter; transcription; translocation
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  Data: 0 (Nuclear Localization Signals)<br />0 (Nuclear Respiratory Factor 1)
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  Data: 10.1016/j.jmb.2026.169920
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  Data: 42398803
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42398803
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      – Type: doi
        Value: 10.1016/j.jmb.2026.169920
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 169920
    Subjects:
      – SubjectFull: Cell Nucleus metabolism
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Active Transport, Cell Nucleus
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Phosphorylation
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      – SubjectFull: Amino Acid Sequence
        Type: general
      – SubjectFull: Nuclear Localization Signals metabolism
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      – SubjectFull: Nuclear Localization Signals genetics
        Type: general
      – SubjectFull: Nuclear Respiratory Factor 1 metabolism
        Type: general
      – SubjectFull: Nuclear Respiratory Factor 1 genetics
        Type: general
      – SubjectFull: Nuclear Respiratory Factor 1 chemistry
        Type: general
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      – TitleFull: Characterization of Diverse Functions of NRF1 Nuclear Localization Sequence.
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              Text: 2026 Oct 01
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