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Title: SENP1 inhibition induces apoptosis and growth arrest of multiple myeloma cells through modulation of NF-κB signaling

SUMO/sentrin specific protease 1 (Senp1) is an important regulation protease in the protein sumoylation, which affects the cell cycle, proliferation and differentiation. The role of Senp1 mediated protein desumoylation in pathophysiological progression of multiple myeloma is unknown. In this study, we demonstrated that Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. Lentivirus-mediated Senp1 knockdown triggers apoptosis and reduces viability, proliferation and colony forming ability of MM cells. The NF-κB family members including P65 and inhibitor protein IkBα play important roles in regulation of MM cell survival and proliferation. We further demonstrated that Senp1 inhibition decreased IL-6-induced P65 and IkBα phosphorylation, leading to inactivation of NF-kB signaling in MM cells. These results delineate a key role for Senp1in IL-6 induced proliferation and survival of MM cells, suggesting it may be a potential new therapeutic target in MM. - Highlights: • Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. • Senp1 knockdown triggers apoptosis and reduces proliferation of MM cells. • Senp1 inhibition decreased IL-6-induced P65 and IkBα phosphorylation.
Authors:
 [1] ;  [2] ; ; ;  [3] ;  [4] ; ;  [5] ;  [3] ;  [3] ;  [2] ;  [3] ;  [2]
  1. Graduate School of Anhui Medical University, Hefei (China)
  2. (China)
  3. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)
  4. Department of Hematology, General Hospital of Air Force, Beijing (China)
  5. Department of Hematology, PLA General Hospital, Beijing (China)
Publication Date:
OSTI Identifier:
22462024
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 460; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; COLONY FORMATION; INACTIVATION; INHIBITION; MODULATION; PHOSPHORYLATION; PLANT GROWTH; PROTEINS; SIGNALS; VIABILITY