alexa Identification of a nuclear localization sequence within the structure of the human interleukin-1 alpha precursor.


Angiology: Open Access

Author(s): Wessendorf JH

Abstract Share this page

Recent studies have suggested that the signal peptide-less cytokine, interleukin (IL)-1 alpha, may play a role as an intracellular regulator of human endothelial cell proliferation in vitro (Garfinkel, S., Haines, D. S., Brown, S., Wessendorf, J., Gillespie, D. H., and Maciag, T. (1992) J. Biol. Chem. 267, 24375-24378). In order to determine the intracellular locale of the IL-1 alpha precursor, we fused the open reading frame of the IL-1 alpha precursor to the reporter gene beta-galactosidase (Gal) and studied the cellular distribution of the chimera in NIH 3T3 cells after transfection. Immunological and enzymatic analysis demonstrated that the IL-1 alpha:beta-Gal fusion protein was associated with the nucleus. To further define the region responsible for this activity, we ligated the mature form of IL-1 alpha (IL-1 alpha 113-271) and the IL-1 alpha precursor domain (IL-1 alpha 1-112) to beta-Gal. Analysis of the intracellular distribution of these chimeric polypeptides following transfection demonstrated a differential distribution of IL-1 alpha 1-112:beta-Gal in the nucleus and IL-1 alpha 113-271:beta-Gal in the cytosol. Because the IL-1 alpha precursor domain contains a sequence that resembles a nuclear translocation signal (KVLKKRRL, residues 79-86), we prepared an IL-1 alpha precursor point mutant in which Lys82 was replaced by Glu. Transfection of NIH 3T3 cells with the IL-1 alpha precursor point mutant (IL-1 alpha 1-271 Glu82:beta-Gal) resulted in a significant reduction in the ability of the IL-1 alpha precursor to associate with the nucleus and similar data were obtained as a result of Lys82 mutagenesis in the IL-1 alpha precursor domain (IL-1 alpha 1-112 Glu82:beta-Gal). These data suggest that the IL-1 alpha precursor contains a functional nuclear localization sequence within the structure of the precursor domain and Lys82 is critical for its function.

  • To read the full article Visit
  • Open Access
This article was published in J Biol Chem and referenced in Angiology: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • International Conference on Vascular Biology & Medicine
    July 24-25, 2017 Chicago, USA
  • International Conference on Angiology
    Oct 16-17, 2017, Budapest, Hungary
  • 21st International Conference on Clinical & Experimental Cardiology
    October 16-18, 2017 Chicago, USA

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version