Oncotarget

Research Papers:

Deptor transcriptionally regulates endoplasmic reticulum homeostasis in multiple myeloma cells

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

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Abstract

Valeria Catena1,*, Tiziana Bruno1,*, Francesca De Nicola1, Frauke Goeman2, Matteo Pallocca1, Simona Iezzi1, Cristina Sorino1, Giovanni Cigliana3, Aristide Floridi1, Giovanni Blandino2, Maurizio Fanciulli1

1SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy

2Epigenetic, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy

3Clinical Pathology Laboratories, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy

*These authors have contributed equally to this work

Correspondence to:

Maurizio Fanciulli, email: maurizio.fanciulli@ifo.gov.it

Keywords: multiple myeloma, deptor, ER stress, homeostasis, transcription

Received: April 29, 2016     Accepted: August 13, 2016     Published: September 16, 2016

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.

Author Information

Valeria Catena

Tiziana Bruno

Francesca De Nicola

Frauke Goeman

Matteo Pallocca

Simona Iezzi

Cristina Sorino

Giovanni Cigliana

Aristide Floridi

Giovanni Blandino

Maurizio Fanciulli
Primary Contact  _


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