![]() These interactions may be direct or they may be mediated by adaptor proteins such as importin α1-α7 (Impα1-Impα7 also known as KPNA1-KPNA7) that recognize and bind to the NLS present in many of the proteins imported by Impβ. The importins mediate transport between the cytoplasm and the nucleus, interacting with their substrates through specific motifs called nuclear localization signals (NLSs). These 90-130 kDa soluble proteins interact with three different elements: the cargo they are going to transport, the nucleoporins and the small GTPase Ran. Although small molecules (smaller than 20-40 kDa) can pass through nuclear pore complexes by passive diffusion, the translocation of the majority of proteins requires energy and in most of the cases, it is mediated by nuclear transport receptors (NTRs) of the importin-β (Impβ also known as KPNB1) family ( Gorlich and Kutay, 1999 Pemberton and Paschal, 2005). Importantly, the identified basic residues are also conserved in other families of C 2H 2 transcription factors whose nuclear localization requires the zinc finger region.Īs transcription factors, Snail proteins must translocate to the nucleus in order to be functional. Interestingly, the consensus residues for importin-binding are also involved in DNA binding, suggesting that importins could prevent non-specific binding of these transcription factors to cytoplasmic polyanions. This NLS is characterized by the presence of basic residues at defined positions in at least three consecutive zinc fingers. Here we show that several importins mediate the nuclear import of the human Snail proteins and we identify a unique nuclear localization signal (NLS), recognized by all the importins, that has been conserved during the evolution of the Snail family. ![]() Given the importance of this gene family in physiology and pathology, it is essential to understand the mechanisms by which Snail proteins are imported into or exported out of the nucleus. The expression of Snail transcription factors is tightly regulated at the transcriptional level and their activity is modulated by their subcellular localization. Snail proteins are C 2H 2 class zinc finger transcription factors involved in different processes during embryonic development, as well as in several adult pathologies including cancer and organ fibrosis.
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