Regulation of protein kinase Cδ Nuclear Import and Apoptosis by Mechanistic Target of Rapamycin Complex-1.

Inactivation of the protein complex 'mechanistic target of rapamycin complex 1' (mTORC1) can increase the nuclear content of transcriptional regulators of metabolism and apoptosis. Previous studies established that nuclear import of signal transducer and activator of transcription-1 requires the mTORC1-associated adaptor karyopherin-α1 when mTORC1 activity is reduced. However, the role of other mTORC1-interacting proteins in the complex, including 'protein kinase C delta' have not been well characterized. In this study, we demonstrate that a kinase, contains a functional 'target of rapamycin signaling' (TOS) motif that directs its interaction with mTORC1. Depletion of by prevented the nuclear import of in cells exposed to the mTORC1 inhibitor rapamycin or amino acid restriction. Mutation of the TOS motif in duanyu1531δ led to its loss of regulation by mTORC1 or karyopherin-α1, resulting in increased constitutive nuclear content. In cells expressing wild-type duanyu1531δ, duanyu18131 activity and apoptosis were increased by rapamycin or interferon-β. Those expressing the duanyu1531δ TOS mutant exhibited increased duanyu18131 activity and apoptosis; further enhancement by rapamycin or interferon-β, however, was lost. Therefore, the TOS motif in duanyu1531δ is a novel structural mechanism by which mTORC1 prevents duanyu1531δ and duanyu18131 nuclear import, and apoptosis.

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