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Synthetic peptides as nuclear localization signals

Nature volume 322, pages 641–644 (1986)Cite this article

Abstract

The nuclear envelope defines a compartment boundary which is penetrated by pores that mediate a remarkable transport process. Precursor RNAs are retained in the nucleus, while processed messenger RNA1, transfer RNA2 and ribosomal subunits3 are transported to the cytoplasm. Proteins destined for the nucleus become localized soon after synthesis and again following mitosis, while cytoplasmic proteins are excluded4. The process is highly specific: a single base change in vertebrate initiator tRNAMet (tRNAimet) reduces the rate of export 20-fold5; a point mutation within the simian virus 40 (SV40) large-T antigen, converting Lys 128 to Thr (ref. 6) or Asn (ref. 7), prevents import. Lys 128 lies within a short ‘signal’ sequence which, when fused to large non-nuclear proteins, causes their accumulation in nuclei6–8. Regions of other eukaryotic proteins also seem to contain nuclear localization signals, although a single consensus sequence has not emerged9–13. We report here that a synthetic peptide containing 10 residues of large-T antigen sequence serves as a nuclear localization signal when cross-linked to bovine serum albumin (BSA) or immunoglobulin G (IgG) and microinjected in Xenopus oocytes. Substitution of Thr at the position of Lys 128 in this peptide renders it six- to sevenfold less effective. The uptake of peptide-linked BSA is saturable, and the rate is diminished by co-injection of free peptide. These findings are indicative of a receptor-mediated uptake process. With the use of anti-peptide antibodies, a family of proteins is revealed in nuclear but not cytoplasmic extracts of human lymphocytes which contain large-T antigen-like sequences.

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Authors and Affiliations

  1. Department of Cell Biology, Stanford University School of Medicine, Stanford, California, 943-5, USA

    David S. Goldfarb & Roger D. Kornberg

  2. Department of Medical Microbiology, Stanford University School of Medicine, Stanford, California, 943-5, USA

    Jean Gariépy & Gary Schoolnik

Authors
  1. David S. Goldfarb
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  2. Jean Gariépy
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  3. Gary Schoolnik
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  4. Roger D. Kornberg
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Goldfarb, D., Gariépy, J., Schoolnik, G. et al. Synthetic peptides as nuclear localization signals. Nature 322, 641–644 (1986). https://doi.org/10.1038/322641a0

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