Molecular basis for specificity of nuclear import and prediction of nuclear localization

Mary Marfori, Andrew Mynott, Jonathan Ellis, Ahmed Mehdi, Neil FW. Saunders, Paul M. Curmi, Jade Forwood, Mikael Boden, Bostjan Kobe

Research output: Contribution to journalArticlepeer-review

279 Citations (Scopus)
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Although proteins are translated on cytoplasmic ribosomes, many of these proteins play essential roles in the nucleus, mediating key cellular processes including but not limited to DNA replication and repair as well as transcription and RNA processing. Thus, understanding how these critical nuclear proteins are accurately targeted to the nucleus is of paramount importance in biology. Interaction and structural studies in the recent years have jointly revealed some general rules on the specificity determinants of the recognition of nuclear targeting signals by their specific receptors, at least for two nuclear import pathways: (i) the classical pathway, which involves the classical nuclear localization sequences (cNLSs) and the receptors importin-'/karyopherin-' and importin-ß/karyopherin-ß1; and (ii) the karyopherin-ß2 pathway, which employs the proline-tyrosine (PY)-NLSs and the receptor transportin-1/karyopherin-ß2. The understanding of specificity rules allows the prediction of protein nuclear localization. We review the current understanding of the molecular determinants of the specificity of nuclear import, focusing on the importin-''cargo recognition, as well as the currently available databases and predictive tools relevant to nuclear localization.
Original languageEnglish
Pages (from-to)1562-1577
Number of pages16
JournalBiochimica et Biophysica Acta: international journal of biochemistry and biophysics
Issue number9
Early online date2010
Publication statusPublished - Sep 2011


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