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Cell signalling

Transcription factors crossing the cell membrane

Nature Reviews Molecular Cell Biology volume 25, page 86 (2024)Cite this article

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Cells in living organisms are encased by lipid membranes, which separate them from aqueous environments. Consequently, cells have developed mechanisms to facilitate the transport of proteins to and from the extracellular space across hydrophobic membranes. A distinct subset of proteins that possess target sequences for intracellular membranous vesicles can exit the cell upon vesicular fusion with the plasma membrane. However, although this mechanism enables proteins to reach the surface of target cells and transmit signals, early studies did not indicate their internalization.

This longstanding model of intercellular protein trafficking was challenged by the discovery of the cell-penetrating ability of Tat protein from the human immunodeficiency virus by Frankel and Pabo. Separately, Alain Prochiantz and colleagues demonstrated the cell-penetrating property of the antennapedia (Antp) protein.

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Original article

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  • Frankel, A. D. & Pabo, C. O. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55, 1189–1193 (1988)

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  • Di Nardo, A. et al. The physiology of homeoprotein transduction. Physiol. Rev. 98, 1943–1982 (2018)

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  1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea

    Jin Woo Kim

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  1. Jin Woo Kim
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Correspondence to Jin Woo Kim.

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Kim, J.W. Transcription factors crossing the cell membrane. Nat Rev Mol Cell Biol 25, 86 (2024). https://doi.org/10.1038/s41580-023-00667-y

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  • DOI: https://doi.org/10.1038/s41580-023-00667-y

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