دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Regulation of protein kinase Cδ Nuclear Import and Apoptosis by Mechanistic Target of Rapamycin Complex-1
المؤلفون: Layoun, Antonio, Goldberg, Alexander A., Baig, Ayesha, Eng, Mikaela, Attias, Ortal, Nelson, Kristoff, Carella, Alexandra, Amberber, Nahomi, Fielhaber, Jill A., Joung, Kwang-Bo, Schmeing, T. Martin, Han, Yingshan, Downey, Jeffrey, Divangahi, Maziar, Roux, Philippe P., Kristof, Arnold S.
المساهمون: Canadian Cancer Society Research Institute, Human Frontier Science Program
المصدر: Scientific Reports ; volume 9, issue 1 ; ISSN 2045-2322
بيانات النشر: Springer Science and Business Media LLC
سنة النشر: 2019
مصطلحات موضوعية: Multidisciplinary
الوصف: 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 (STAT1) requires the mTORC1-associated adaptor karyopherin-α1 (KPNA1) when mTORC1 activity is reduced. However, the role of other mTORC1-interacting proteins in the complex, including ‘protein kinase C delta’ (PKCδ), have not been well characterized. In this study, we demonstrate that PKCδ, a STAT1 kinase, contains a functional ‘target of rapamycin signaling’ (TOS) motif that directs its interaction with mTORC1. Depletion of KPNA1 by RNAi prevented the nuclear import of PKCδ in cells exposed to the mTORC1 inhibitor rapamycin or amino acid restriction. Mutation of the TOS motif in PKCδ led to its loss of regulation by mTORC1 or karyopherin-α1, resulting in increased constitutive nuclear content. In cells expressing wild-type PKCδ, STAT1 activity and apoptosis were increased by rapamycin or interferon-β. Those expressing the PKCδ TOS mutant exhibited increased STAT1 activity and apoptosis; further enhancement by rapamycin or interferon-β, however, was lost. Therefore, the TOS motif in PKCδ is a novel structural mechanism by which mTORC1 prevents PKCδ and STAT1 nuclear import, and apoptosis.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1038/s41598-019-53909-5
الإتاحة: https://doi.org/10.1038/s41598-019-53909-5Test
https://www.nature.com/articles/s41598-019-53909-5.pdfTest
https://www.nature.com/articles/s41598-019-53909-5Test
حقوق: https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test
رقم الانضمام: edsbas.9E8D191F
قاعدة البيانات: BASE