title: Deptor transcriptionally regulates endoplasmic reticulum homeostasis in multiple myeloma cells.
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.
authors.affiliation: SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Catena
authors.affiliation: SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bruno
authors.affiliation: SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Nicola
authors.affiliation: Epigenetic, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Frauke
authors.initials: F
authors.lastname: Goeman
authors.affiliation: SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pallocca
authors.affiliation: SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Iezzi
authors.affiliation: SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sorino
authors.affiliation: Clinical Pathology Laboratories, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cigliana
authors.affiliation: SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Aristide
authors.initials: A
authors.lastname: Floridi
authors.affiliation: Epigenetic, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
authors.affiliation: SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fanciulli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000069286:Bortezomib / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004721:Endoplasmic Reticulum; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D000069286:Bortezomib; C556139:DEPTOR protein, human
keywords: ER stress; deptor; homeostasis; multiple myeloma; transcription