Deptor transcriptionally regulates endoplasmic reticulum homeostasis in multiple myeloma cells

Valeria Catena, Tiziana Bruno, Francesca De Nicola, Frauke Inger Karen Goeman, Matteo Pallocca, Simona Iezzi, Cristina Sorino, Giovanni Cigliana, Aristide Floridi, Giovanni Blandino, Maurizio Fanciulli

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple myeloma (MM) is a malignant disorder of plasma cells characterized by active production and secretion of monoclonal immunoglobulins (IgG), thus rendering cells prone to endoplasmic reticulum (ER) stress. For this reason, MM cell survival requires to maintain ER homeostasis at basal levels. Deptor is an mTOR binding protein, belonging to the mTORC1 and mTORC2 complexes. It was reported that Deptor is overexpressed in MM cells where it inhibits mTOR kinase activity and promotes cell survival by activating Akt signaling. Here we identify Deptor as a nuclear protein, able to bind DNA and regulate transcription in MM cells. In particular, we found that Deptor plays an important role in the maintenance of the ER network, sustaining the expression of several genes involved in this pathway. In agreement with this, Deptor depletion induces ER stress and synergizes the effect of the proteasome inhibitor bortezomib (Bz) in MM cells. These findings provide important new insights in the ER stress control in MM cells.

Original languageEnglish
Pages (from-to)70546-70558
Number of pages13
JournalOncotarget
Volume7
Issue number43
DOIs
Publication statusPublished - 2016

Keywords

  • Deptor
  • ER stress
  • Homeostasis
  • Multiple myeloma
  • Transcription

ASJC Scopus subject areas

  • Oncology

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