Targeting nuclear import shuttles, importins/karyopherins alpha by a peptide mimicking the NFκB1/p50 nuclear localization sequence

Journal of the American Heart Association

Volumn 2, Issue 5, 2013, Pages

  Zienkiewicz, Jozef ^a   Armitage, Amy ^a,b   Hawiger, Jacek ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NORTHERN VIRGINIA COMMUNITY COLLEGE   (United States)

Author keywords

Cell penetrating peptide; Importin; Importin a diversity region; Karyopherin; NF B; Nuclear import adaptors; Nuclear transport; Steatohepatitis; Transcription factor; Vascular inflammation

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; KARYOPHERIN 5ALPHA; KARYOPHERIN ALPHA; N50 PEPTIDE; PEPTIDE DERIVATIVE; UNCLASSIFIED DRUG; CELL PENETRATING PEPTIDE; CSN50.1 PEPTIDE; NUCLEAR LOCALIZATION SIGNAL; KARYOPHERIN; TRANSCRIPTION FACTOR;

ARTICLE; BINDING AFFINITY; CELL NUCLEUS; COMPARATIVE STUDY; COMPUTER MODEL; CONTROLLED STUDY; HUMAN; HUMAN CELL; HYDROPHILICITY; INFLAMMATION; INTRACELLULAR TRANSPORT; MOLECULAR DOCKING; NUCLEAR IMPORT; NUCLEAR LOCALIZATION SIGNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TARGETING; PROTEIN TRANSPORT; STOICHIOMETRY; STRUCTURE ANALYSIS; ACTIVE TRANSPORT; CELL CULTURE; METABOLISM; PHYSIOLOGY; CELL-PENETRATING PEPTIDE; IMPORTIN Α DIVERSITY REGION; NFΚB; NUCLEAR IMPORT ADAPTORS; NUCLEAR TRANSPORT; STEATOHEPATITIS; VASCULITIS;

ACTIVE TRANSPORT, CELL NUCLEUS; ALPHA KARYOPHERINS; CELL NUCLEUS; CELL-PENETRATING PEPTIDES; CELLS, CULTURED; HUMANS; NF-KAPPA B P50 SUBUNIT; NUCLEAR LOCALIZATION SIGNALS;

CELL-PENETRATING PEPTIDE; IMPORTIN; IMPORTIN Α DIVERSITY REGION; KARYOPHERIN; NFΚB; NUCLEAR IMPORT ADAPTORS; NUCLEAR TRANSPORT; STEATOHEPATITIS; TRANSCRIPTION FACTOR; VASCULAR INFLAMMATION;

EID: 84891713350     PISSN: None     EISSN: 20479980     Source Type: Journal    
DOI: 10.1161/JAHA.113.000386     Document Type: Article

References (51)

1. Liu Y, Major AS, Zienkiewicz J, Gabriel CL, Veach RA, Moore DJ, Collins RD, Hawiger J. Nuclear transport modulation reduces hypercholesterolemia, atherosclerosis, and fatty liver. J Am Heart Assoc. 2013;2:e000093.
2. Lin YZ, Yao SY, Veach RA, Torgerson TR, Hawiger J. Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J Biol Chem. 1995;270:14255-14258.
3. Torgerson TR, Colosia AD, Donahue JP, Lin YZ, Hawiger J. Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50. J Immunol. 1998;161:6084-6092.
4. Hawiger J. Innate immunity and inflammation: a transcriptional paradigm. Immunol Res. 2001;23:99-109.
5. Veach RA, Liu D, Yao S, Chen Y, Liu XY, Downs S, Hawiger J. Receptor/transporter-independent targeting of functional peptides across the plasma membrane. J Biol Chem. 2004;279:11425-11431.
6. Orange JS, May MJ. Cell penetrating peptide inhibitors of nuclear factor-kappa B. Cell Mol Life Sci. 2008;65:3564-3591.
7. Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, Goldstein JL. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci USA. 2003;100:12027-12032.
8. Lee SJ, Sekimoto T, Yamashita E, Nagoshi E, Nakagawa A, Imamoto N, Yoshimura M, Sakai H, Chong KT, Tsukihara T, Yoneda Y. The structure of importin-beta bound to SREBP-2: nuclear import of a transcription factor. Science. 2003;302:1571-1575.
9. Notredame C, Higgins DG, Heringa J. T-coffee: a novel method for fast and accurate multiple sequence alignment. J Mol Biol. 2000;302:205-217.
10. Lin Q, Liu Y, Moore DJ, Elizer SK, Veach RA, Hawiger J, Ruley HE. Cutting edge: the "death" adaptor CRADD/RAIDD targets BCL10 and suppresses agonist-induced cytokine expression in T lymphocytes. J Immunol. 2012;188:2493-2497.
11. Trott O, Olson AJ. Autodock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31:455-461.
12. Sanner MF. Python: a programming language for software integration and development. J Mol Graph Model. 1999;17:57-61.
13. Morris GM, Huey R, Olson AJ. Using autodock for ligand-receptor docking. Curr Protoc Bioinformatics. 2008; Chapter 8: Unit 8 14.
14. Timney BL, Tetenbaum-Novatt J, Agate DS, Williams R, Zhang W, Chait BT, Rout MP. Simple kinetic relationships and nonspecific competition govern nuclear import rates in vivo. J Cell Biol. 2006;175:579-593.
15. Donald R, Ballard DW, Hawiger J. Proteolytic processing of NF-B/IB in human monocytes: ATP-dependent induction by pro-inflammatory mediators. J Biol Chem. 1995;270:9-12.
16. Ganchi PA, Sun SC, Greene WC, Ballard DW. I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding. Mol Biol Cell. 1992;3: 1339-1352.
17. Chen Z, Hagler J, Palombella VJ, Melandri F, Scherer D, Ballard D, Maniatis T. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 1995;9:1586-1597.
18. Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. Proc Natl Acad Sci USA. 1995;92:11259-11263.
19. Groll M, Kim KB, Kairies N, Huber R, Crews CM. Crystal structure of epoxomicin: 20s proteasome reveals a molecular basis for selectivity of alpha', beta'-epoxyketone proteasome inhibitors. J Am Chem Soc. 2000;122:1237-1238.
20. Hawiger J. Cellular import of functional peptides to block intracellular signaling. Curr Opin Immunol. 1997;9:189-194.
21. Lott K, Cingolani G. The importin beta binding domain as a master regulator of nucleocytoplasmic transport. Biochim Biophys Acta. 2011;1813:1578-1592.
22. Fontes MRM, Teh T, Toth G, John A, Pavo I, Jans DA, Kobe B. Role of flanking sequences and phosphorylation in the recognition of the simian-virus-40 large T-antigen nuclear localization sequences by importin-alpha. Biochem J. 2003; 375:339-349.
23. Newmeyer DD, Forbes DJ. Nuclear import can be separated into distinct steps in vitro: nuclear pore binding and translocation. Cell. 1988;52:641-653.
24. Richardson WD, Mills AD, Dilworth SM, Laskey RA, Dingwall C. Nuclear protein migration involves two steps: rapid binding at the nuclear envelope followed by slower translocation through nuclear pores. Cell. 1988;52:655-664.
25. Akey CW, Goldfarb DS. Protein import through the nuclear pore complex is a multistep process. J Cell Biol. 1989;109:971-982.
26. Jans DA, Hubner S. Regulation of protein transport to the nucleus: central role of phosphorylation. Physiol Rev. 1996;76:651-685.
27. Kalderon D, Roberts BL, Richardson WD, Smith AE. A short amino acid sequence able to specify nuclear location. Cell. 1984;39:499-509.
28. Lanford RE, Butel JS. Construction and characterization of an SV40 mutant defective in nuclear transport of T antigen. Cell. 1984;37:801-813.
29. Dingwall C, Laskey RA. Nuclear targeting sequences-a consensus? Trends Biochem Sci. 1991;16:478-481.
30. Kalderon D, Richardson WD, Markham AF, Smith AE. Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature. 1984;311: 33-38.
31. Robbins J, Dilwortht SM, Laskey RA, Dingwall C. Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence. Cell. 1991;64:615-623.
32. Kohler M, Speck C, Christiansen M, Bischoff FR, Prehn S, Haller H, Gorlich D, Hartmann E. Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import. Mol Cell Biol. 1999;19:7782-7791.
33. Friedrich B, Quensel C, Sommer T, Hartmann E, Kohler M. Nuclear localization signal and protein context both mediate importin alpha specificity of nuclear import substrates. Mol Cell Biol. 2006;26:8697-8709.
34. Conti E, Uy M, Leighton L, Blobel G, Kuriyan J. Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin alpha. Cell. 1998;94:193-204.
35. Fontes MR, Teh T, Kobe B. Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-alpha. J Mol Biol. 2000;297:1183-1194.
36. Fontes MR, Teh T, Jans D, Brinkworth RI, Kobe B. Structural basis for the specificity of bipartite nuclear localization sequence binding by importin-alpha. J Biol Chem. 2003;278:27981-27987.
37. Catimel B, Teh T, Fontes MR, Jennings IG, Jans DA, Howlett GJ, Nice EC, Kobe B Biophysical characterization of interactions involving importin-alpha during nuclear import. J Biol Chem. 2001;276:34189-34198.
38. Sekimoto T, Imamoto N, Nakajima K, Hirano T, Yoneda Y. Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1. EMBO J. 1997;16:7067-7077.
39. Nardozzi J, Wenta N, Yasuhara N, Vinkemeier U, Cingolani G. Molecular basis for the recognition of phosphorylated STAT1 by importin alpha5. J Mol Biol. 2010;402:83-100.
40. Theodore M, Kawai Y, Yang J, Kleshchenko Y, Reddy SP, Villalta F, Arinze IJ. Multiple nuclear localization signals function in the nuclear import of the transcription factor Nrf2. J Biol Chem. 2008;283:8984-8994.
41. Fagerlund R, Kinnunen L, Köhler M, Julkunen I, Melèn K. NF-κB is transported into the nucleus by importin α3 and importin α4. J Biol Chem. 2005;280:15942-15951.
42. Fagerlund R, Melèn K, Cao X, Julkunen I. NF-κB p52, RelB and c-Rel are transported into the nucleus via a subset of importin a molecules. Cell Signal. 2008;20:1442-1451.
43. Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, Hunninghake GM, Vera MP, Blackwell TS, Baron RM, Feinberg MW. Microrna-181b regulates NF-kappaB-mediated vascular inflammation. J Clin Invest. 2012;122:1973-1990.
44. Liu XY, Robinson D, Veach RA, Liu D, Timmons S, Collins RD, Hawiger J. Peptide-directed suppression of a pro-inflammatory cytokine response. J Biol Chem. 2000;275:16774-16778.
45. Liu D, Li C, Chen Y, Burnett C, Liu XY, Downs S, Collins RD, Hawiger J. Nuclear import of proinflammatory transcription factors is required for massive liver apoptosis induced by bacterial lipopolysaccharide. J Biol Chem. 2004; 279:48434-48442.
46. Liu D, Zienkiewicz J, DiGiandomenico A, Hawiger J. Suppression of acute lung inflammation by intracellular peptide delivery of a nuclear import inhibitor. Mol Ther. 2009;17:796-802.
47. Duffy JY, McLean KM, Lyons JM, Czaikowski AJ, Wagner CJ, Pearl JM. Modulation of nuclear factor-kappaB improves cardiac dysfunction associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. Crit Care Med. 2009;37:577-583.
48. O'Sullivan AW, Wang JH, Redmond HP. NF-jB and p38 MAPK inhibition improve survival in endotoxin shock and in a cecal ligation and puncture model of sepsis in combination with antibiotic therapy. J Surg Res. 2009; 152:46-53.
49. Moore DJ, Zienkiewicz J, Kendall PL, Liu D, Liu X, Veach RA, Collins RD, Hawiger J. In vivo islet protection by a nuclear import inhibitor in a mouse model of type 1 diabetes. PLoS One. 2010;5:e13235.
50. Veach RA, Zienkiewicz J, Collins RD, Hawiger J. Lethality in a murine model of pulmonary anthrax is reduced by combining nuclear transport modifier with antimicrobial therapy. PLoS One. 2012;7:e30527.
51. Shmidt T, Hampich F, Ridders M, Schultrich S, Hans VH, Tenner K, Vilianovich L, Qadri F, Alenina N, Hartmann E, Kohler M, Bader M. Normal brain development in importin-alpha5 deficient-mice. Nat Cell Biol. 2007;9:1337-1338; author reply 1339.