Extracellular Signal-dependent Nuclear Import of Stat1 is Mediated by Nuclear Pore-targeting Complex Formation with NPI-1, but Not Rch1

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1998 Jan 31

PMID 9384585

Citations 134

Authors

T Sekimoto

N Imamoto

K Nakajima

T Hirano

Y Yoneda

Affiliations

Soon will be listed here.

Abstract

In response to interferon-gamma (IFN-gamma), Stat1 is tyrosine phosphorylated and translocates to the nucleus where it activates transcription. In this study, we identified factors which mediate the nuclear import of Stat1. Tyrosine-phosphorylated Stat1 associated with the beta subunit (a 97 kDa component) of the nuclear pore-targeting complex via the NPI-1 family, but not the Rch1 family, of alpha subunit (a 58 kDa component) as a result of IFN-gamma stimulation. Antibodies against NPI-1 or beta subunit consistently inhibited the IFN-gamma-dependent nuclear import of Stat1 in living cells, although antibodies reactive to Rch1 had no effect. Solution binding assays with deletion mutants of NPI-1 showed that the Stat1-binding domain of NPI-1 was located in the carboxy-terminal region, which is clearly distinct from the SV40 large T antigen nuclear localization signal (NLS)-binding region. These results indicate that the extracellular signal-dependent nuclear transport of Stat1 is mediated by NPI-1, but not Rch1, in conjunction with beta subunit, and that these factors participate in, not only constitutive, but also the conditional nuclear import of proteins.

Citing Articles

Importin-7-dependent nuclear translocation of the Flavivirus core protein is required for infectious virus production.

Itoh Y, Miyamoto Y, Tokunaga M, Suzuki T, Takada A, Ninomiya A PLoS Pathog. 2024; 20(8):e1012409.

PMID: 39146232 PMC: 11326614. DOI: 10.1371/journal.ppat.1012409.

Importin Alpha 1 (Dα1) Is Required to Maintain Germline Stem Cells in the Testis Niche.

Heaney J, Zhao J, Casagranda F, Loveland K, Siddall N, Hime G Cells. 2024; 13(6.

PMID: 38534338 PMC: 10969130. DOI: 10.3390/cells13060494.

Upping the ante: enhanced expression of interferon-antagonizing ORF6 and ORF9b proteins by SARS-CoV-2 variants of concern.

Caobi A, Saeed M Curr Opin Microbiol. 2024; 79:102454.

PMID: 38518551 PMC: 11162932. DOI: 10.1016/j.mib.2024.102454.

SARS-CoV-2 Orf6 is positioned in the nuclear pore complex by Rae1 to inhibit nucleocytoplasmic transport.

Makio T, Zhang K, Love N, Mast F, Liu X, Elaish M Mol Biol Cell. 2024; 35(5):ar62.

PMID: 38507240 PMC: 11151100. DOI: 10.1091/mbc.E23-10-0386.

Viral Targeting of Importin Alpha-Mediated Nuclear Import to Block Innate Immunity.

Vogel O, Forwood J, Leung D, Amarasinghe G, Basler C Cells. 2024; 13(1).

PMID: 38201275 PMC: 10778312. DOI: 10.3390/cells13010071.

References

Melchior F, Gerace L . Mechanisms of nuclear protein import. Curr Opin Cell Biol. 1995; 7(3):310-8. DOI: 10.1016/0955-0674(95)80084-0. View

Imamoto N, Shimamoto T, Takao T, Tachibana T, Kose S, Matsubae M . In vivo evidence for involvement of a 58 kDa component of nuclear pore-targeting complex in nuclear protein import. EMBO J. 1995; 14(15):3617-26. PMC: 394435. DOI: 10.1002/j.1460-2075.1995.tb00031.x. View

Gorlich D, Mattaj I . Nucleocytoplasmic transport. Science. 1996; 271(5255):1513-8. DOI: 10.1126/science.271.5255.1513. View

Dingwall C, Laskey R . Nuclear targeting sequences--a consensus?. Trends Biochem Sci. 1991; 16(12):478-81. DOI: 10.1016/0968-0004(91)90184-w. View

Yano R, Oakes M, Yamaghishi M, Dodd J, Nomura M . Cloning and characterization of SRP1, a suppressor of temperature-sensitive RNA polymerase I mutations, in Saccharomyces cerevisiae. Mol Cell Biol. 1992; 12(12):5640-51. PMC: 360503. DOI: 10.1128/mcb.12.12.5640-5651.1992. View

Shuai K, Schindler C, Prezioso V, Darnell Jr J . Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science. 1992; 258(5089):1808-12. DOI: 10.1126/science.1281555. View

Sadowski H, Shuai K, Darnell Jr J, Gilman M . A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. Science. 1993; 261(5129):1739-44. DOI: 10.1126/science.8397445. View

Shuai K, Stark G, Kerr I, Darnell Jr J . A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science. 1993; 261(5129):1744-6. DOI: 10.1126/science.7690989. View

Moore M, Blobel G . The GTP-binding protein Ran/TC4 is required for protein import into the nucleus. Nature. 1993; 365(6447):661-3. DOI: 10.1038/365661a0. View

10.

Shuai K, Ziemiecki A, Wilks A, Harpur A, Sadowski H, Gilman M . Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature. 1993; 366(6455):580-3. DOI: 10.1038/366580a0. View

11.

Melchior F, Paschal B, Evans J, Gerace L . Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor. J Cell Biol. 1993; 123(6 Pt 2):1649-59. PMC: 2290879. DOI: 10.1083/jcb.123.6.1649. View

12.

Shuai K, Horvath C, Huang L, Qureshi S, Cowburn D, Darnell Jr J . Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell. 1994; 76(5):821-8. DOI: 10.1016/0092-8674(94)90357-3. View

13.

Zhong Z, Wen Z, Darnell Jr J . Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994; 264(5155):95-8. DOI: 10.1126/science.8140422. View

14.

Akira S, Nishio Y, Inoue M, Wang X, Wei S, Matsusaka T . Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell. 1994; 77(1):63-71. DOI: 10.1016/0092-8674(94)90235-6. View

15.

Darnell Jr J, Kerr I, Stark G . Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994; 264(5164):1415-21. DOI: 10.1126/science.8197455. View

16.

Cuomo C, Kirch S, Gyuris J, Brent R, Oettinger M . Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein. Proc Natl Acad Sci U S A. 1994; 91(13):6156-60. PMC: 44157. DOI: 10.1073/pnas.91.13.6156. View

17.

Fujitani Y, Nakajima K, Kojima H, Nakae K, Takeda T, Hirano T . Transcriptional activation of the IL-6 response element in the junB promoter is mediated by multiple Stat family proteins. Biochem Biophys Res Commun. 1994; 202(2):1181-7. DOI: 10.1006/bbrc.1994.2053. View

18.

Cortes P, Ye Z, Baltimore D . RAG-1 interacts with the repeated amino acid motif of the human homologue of the yeast protein SRP1. Proc Natl Acad Sci U S A. 1994; 91(16):7633-7. PMC: 44456. DOI: 10.1073/pnas.91.16.7633. View

19.

Moore M, Blobel G . Purification of a Ran-interacting protein that is required for protein import into the nucleus. Proc Natl Acad Sci U S A. 1994; 91(21):10212-6. PMC: 44988. DOI: 10.1073/pnas.91.21.10212. View

20.

Gorlich D, Prehn S, Laskey R, Hartmann E . Isolation of a protein that is essential for the first step of nuclear protein import. Cell. 1994; 79(5):767-78. DOI: 10.1016/0092-8674(94)90067-1. View