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 language | English |
|---|---|
| Pages (from-to) | 70546-70558 |
| Number of pages | 13 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 43 |
| DOIs | |
| Publication status | Published - 2016 |
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Keywords
- Deptor
- ER stress
- Homeostasis
- Multiple myeloma
- Transcription
ASJC Scopus subject areas
- Oncology
Cite this
Deptor transcriptionally regulates endoplasmic reticulum homeostasis in multiple myeloma cells. / Catena, Valeria; Bruno, Tiziana; De Nicola, Francesca; Goeman, Frauke Inger Karen; Pallocca, Matteo; Iezzi, Simona; Sorino, Cristina; Cigliana, Giovanni; Floridi, Aristide; Blandino, Giovanni; Fanciulli, Maurizio.
In: Oncotarget, Vol. 7, No. 43, 2016, p. 70546-70558.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Deptor transcriptionally regulates endoplasmic reticulum homeostasis in multiple myeloma cells
AU - Catena, Valeria
AU - Bruno, Tiziana
AU - De Nicola, Francesca
AU - Goeman, Frauke Inger Karen
AU - Pallocca, Matteo
AU - Iezzi, Simona
AU - Sorino, Cristina
AU - Cigliana, Giovanni
AU - Floridi, Aristide
AU - Blandino, Giovanni
AU - Fanciulli, Maurizio
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Deptor
KW - ER stress
KW - Homeostasis
KW - Multiple myeloma
KW - Transcription
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UR - http://www.scopus.com/inward/citedby.url?scp=84994338967&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.12060
DO - 10.18632/oncotarget.12060
M3 - Article
AN - SCOPUS:84994338967
VL - 7
SP - 70546
EP - 70558
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 43
ER -