The notch pathway promotes NF-κB activation through Asb2 in T cell acute lymphoblastic leukemia cells

• Autorzy: Wu W. , Nie L. , Zhang L. , LI Y.
• Języki publikacji: EN

Abstrakty

EN

Background: Oncogenic Notch1 is known to activate the NF-κB pathway in T cell acute lymphoblastic leukemia (T-ALL) and to up-regulate the transcription of Asb2α, a specificity factor for an E3 ubiquitin ligase complex that plays an important role in hematopoietic differentiation. Therefore, we hypothesize that Notch1 might regulate the NF-κB pathway through Asb2α. Methods: The study involved down-regulation of Notch1 in T-ALL cell lines (CCRFCEM cells and MOLT-4 cells) through treatment with gamma-secretase inhibitor (GSI) as well as the modulation of Asb2 in CCRF-CEM cells and MOLT-4 cells through transduction with lentivirus carrying Asb2 or Asb2-shRNA. Experiments using real-time PCR, western blot and co-immunoprecipitation were performed to evaluate the expression levels of related genes. Cell proliferation and apoptosis were measured while the expression of Asb2 was enhanced or inhibited. Results: Here, we demonstrated for the first time that Notch1 can activate the transcription of Asb2α, which then stimulates activation of NF-κB in T-ALL cells. Asb2α exerts its effects by inducing degradation and dissociation of IκBα from NF-κB in T-ALL cells. Moreover, specific suppression of Asb2α expression can promote apoptosis and inhibit proliferation of T-ALL cells. Conclusion: Notch1 modulates the NF-κB pathway through Asb2α, indicating that Asb2α inhibition is a promising option for targeted therapy against T-ALL.

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2018
• Tom: 23
• Opis fizyczny: p.1-13,fig.,ref.

Twórcy

autor

Wu W.

• Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China

autor

Nie L.

• Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China

autor

Zhang L.

• Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China

autor

LI Y.

• Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, People’s Republic of China

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Identyfikatory

DOI

10.1186/s11658-018-0102-4