SENP2-NDR2-p21 axis modulates lung cancer cell growth.
Eur J Pharmacol
; 978: 176761, 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-38908669
ABSTRACT
Sentrin/small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) perform pivotal roles in SUMO maturation and recycling, which modulate the balance of SUMOylation/de-SUMOylation and spatiotemporal functions of SUMOylation targets. The malfunction of SENPs often results in cellular dysfunction and various diseases. However, studies rarely investigated the correlation between SENP2 and lung cancer. This study revealed that SENP2 is a required contributor to lung cancer-cell growth and targets nuclear Dbf2-related 2 (NDR2, also known as serine/threonine kinase 38L or STK38L) for de-SUMOylation, which improves NDR2 kinase activity. This condition leads to the instability of downstream target p21 in accelerating the G1/S cell cycle transition and suggests SENP2 as a promising therapeutic target for lung cancer in the future. Specifically, astragaloside IV, an active ingredient of Jinfukang Oral Liquid (JOL, a clinical combination antilung cancer drug approved by the National Food and Drug Administration (FDA) of China), can repress lung cancer-cell growth via the SENP2-NDR2-p21 axis, which provides new insights into the molecular mechanism of JOL for lung cancer treatment.
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Base de dados:
MEDLINE
Assunto principal:
Cisteína Endopeptidases
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Proliferação de Células
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Inibidor de Quinase Dependente de Ciclina p21
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Sumoilação
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Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article