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

Xu, J.; Sun, H.-Y.; Xiao, F.-J.; Wang, H.; Yang, Y.; Wang, L.; Gao, C.-J.; Guo, Z.-K.; Wu, C.-T.; Wang, L.-S.

Biochemical and Biophysical Research Communications 460(2): 409-415

2015


ISSN/ISBN: 1090-2104
PMID: 25791478
DOI: 10.1016/j.bbrc.2015.03.047
Accession: 058797470

Download citation:  
Text
  |  
BibTeX
  |  
RIS

Article/Abstract emailed within 0-6 h
Payments are secure & encrypted
Powered by Stripe
Powered by PayPal

Abstract
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-кB 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.