Regulation of karyopherin α1 and nuclear import by mammalian target of rapamycin.

Under conditions of reduced mitogen or nutritional substrate levels, the serine/threonine kinase target of rapamycin can augment the nuclear content of distinct transcription factors and promote the induction of stress response genes. In its latent (i.e., unphosphorylated) form, the transcription factor regulates a subset of genes involved in immune modulation and apoptosis. Based on previous work indicating a functional relationship between mammalian target of rapamycin (mTOR) and the nuclear content of latent we investigated the mechanism by which mTOR controls duanyu18131 nuclear import. By fluorescence confocal microscopy, inactivation of mTOR with rapamycin promoted the nuclear translocation of unphosphorylated duanyu18131, but not that of a duanyu18131 mutant incapable of binding its nuclear import adaptor karyopherin-α1 By immunoprecipitation, was physically associated with mTOR and duanyu18131 in a complex that translocated to the nucleus in response to rapamycin. Although mTOR is not a kinase for the mTOR-associated phosphatase protein phosphatase 2A catalytic interacted directly with Kduanyu15351 and regulated nuclear import of the complex. Kduanyu15351, or its interaction with duanyu18131, was required for the nuclear import of latent duanyu18131, transcriptional induction of the duanyu18131 gene, and caspase-3 activation under conditions of reduced mTOR activity (i.e. rapamycin, glucose starvation, serum withdrawal). Therefore, at low mitogen or nutrient levels, mTOR and protein phosphatase 2A catalytically control the constitutive nuclear import of latent duanyu18131 by Kduanyu15351, which are key modulators of duanyu18131 expression and apoptosis.

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