Perilous traffic

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Science  09 Aug 2019:
Vol. 365, Issue 6453, pp. 555-556
DOI: 10.1126/science.365.6453.555-e

Proper trafficking of proteins across the nuclear envelope is essential for many cellular functions. A subset of human cancers harbor somatic mutations in the XPO1 gene, which encodes exportin-1, part of the cell machinery regulating nuclear export. These genomic data suggest that disruption of nucleocytoplasmic trafficking might contribute to tumorigenesis. Taylor et al. studied the functional consequences of the most recurrent XPO1 mutations and found that the mutations are sufficient to drive oncogenic transformation in model systems. Mechanistically, the mutations alter the ability of exportin-1 to engage protein cargo for nuclear export, which in turn alters the nucleocytoplasmic distribution of hundreds of proteins. Several of these proteins are components of key signaling pathways that regulate cell proliferation.

Cancer Discov. 10.1158/2159-8290.CD-19-0298 (2019).

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