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

Biochemical and Biophysical Research Communications
Jun XuLi-Sheng Wang

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.

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Citations

Dec 24, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Wenwen ZhangLisheng Wang
Jan 31, 2017·Nature Reviews. Cancer·Jacob-Sebastian Seeler, Anne Dejean
Nov 24, 2016·Molecular Aspects of Medicine·James ChonMartha S Field
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Nov 9, 2016·The Journal of Experimental Medicine·Priti AzadGabriel G Haddad
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Aug 14, 2019·International Journal of Molecular Sciences·Mathias BoulangerGuillaume Bossis
May 3, 2019·Acta Crystallographica. Section F, Structural Biology Communications·Nigus D Ambaye
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Apr 4, 2019·European Journal of Pharmacology·Xiaoyu GaoXiaoshan Feng
May 1, 2021·Cancers·Paulina Tokarz, Katarzyna Woźniak

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