SENP1 inhibition induces apoptosis and growth arrest of multiple myeloma cells through modulation of NF-κB signaling.
Biochem Biophys Res Commun
; 460(2): 409-15, 2015 May 01.
Article
em En
| MEDLINE
| ID: mdl-25791478
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endopeptidases
/
Transdução de Sinais
/
Divisão Celular
/
NF-kappa B
/
Apoptose
/
Mieloma Múltiplo
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article