Arginine/Lysine-rich Nuclear Localization Signals Mediate Interactions between Dimeric STATs and Importin α5
Open accessAbstract
Interferon stimulation results in tyrosine phosphorylation, dimerization, and nuclear import of STATs (signal transducers and activators of transcription). Proteins to be targeted into the nucleus usually contain nuclear localization signals (NLSs), which interact with importin alpha. Importin alpha binds to importin beta, which docks the protein complex to nuclear pores, and the complex translocates into the nucleus. Here we show that baculovirus-produced and -activated STAT1 homodimers and STAT1-STAT2 heterodimers directly interacted with importin alpha 5 (NPI-1). This interaction was very stable and was dependent on lysines 410 and 413 of STAT1. Only STAT dimers that had two intact NLS elements, one in each monomer, were able to bind to importin alpha 5. STAT-importin alpha 5 complexes apparently consisted of two STAT and two importin alpha molecules. STAT NLS-dependent colocalization of importin alpha 5 with STAT1 or STAT2 was seen in the nucleus of transfected cells. gamma-Activated sequence DNA elements efficiently inhibited STAT binding to importin alpha 5 suggesting that the DNA and importin alpha binding sites are close to each other in STAT dimers. Our results demonstrate that specific NLSs in STATs mediate direct interactions of STAT dimers with importin alpha, which activates the nuclear import process.
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Nuclear accumulation depends on the integrity of the DNA-binding domain, attributable to the need for a functional dsNLS located there.
“Nuclear accumulation was shown to depend on the integrity of the DNA-binding domain, which can be attributed to the need for a functional dsNLS located here (Fagerlund et al. 2002;Meyer et al. 2002a).”
From DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 (2003) · cites this paper as Fagerlund et al. 2002
A dimer-specific nuclear localization signal comprising residues 407-413 in the DNA-binding domain mediates binding of Stat1 dimers to importin α/β and subsequent nuclear import.
“Recently, we and others described an unusual dimer-specific nuclear localization signal (dsNLS) comprising residues 407-413 in the DNA-binding domain that mediates binding of Stat1 dimers to importin ␣/ and subsequent nuclear import (Fagerlund et al. 2002;McBride et al. 2002;Meyer et al. 2002a).”
From DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 (2003) · cites this paper as Fagerlund et al. 2002
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- Authors
- Fagerlund, R., Melén, K., Kinnunen, L., & Julkunen, I.
- Corresponding author
- Fagerlund, Riku
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 277
- Issue
- 33
- Pages
- 30072-30078
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2058363464
- Cited by
- 183
- References
- 0
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 8 · 2021: 8 · 2020: 4 · 2019: 10 · 2018: 2 · 2017: 4 · 2016: 8 · 2015: 5 · 2014: 10 · 2013: 9 · 2012: 6
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- STAT1, STAT2, nuclear localization signal, nuclear import, interferon signaling, tyrosine phosphorylation, protein-protein interaction, nuclear pore complex
- MeSH terms
- Animals, Arginine, Base Sequence, Cell Line, Chromatography, Gel, DNA-Binding Proteins, Humans, Lysine, Phosphorylation, Protein Binding, Tyrosine, Trans-Activators, Baculoviridae, DNA Primers, Spodoptera, Dimerization, Nuclear Localization Signals, alpha Karyopherins, STAT1 Transcription Factor, STAT2 Transcription Factor
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