BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death

Boh Ram Kim, Youngjoo Kwon, Seung Bae Rho

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) protein is activated in various types of tumors and associated with cancer development and tumor progression. However, the working role of BMI-1 in cellular signaling is not understood completely. In this study, we revealed one possible biologic mechanism of BMI-1 in cancer progression in vitro using a human ovarian tumor cell system. Suppressor of MEK1 (sMEK1), a pivotal regulator involved in the cellular biological response mechanism, was identified as a BMI-1-binding protein. Ectopic expression of BMI-1 activated cell growth by reducing sMEK1-stimulated apoptotic cell death and suppressing p21, p27 and p53 expression, while enhancing cyclin D1, CDK4 and Bcl-2 expression. The effect of BMI-1 on cell cycle and apoptotic regulatory proteins was also confirmed via silencing of BMI-1 expression. Subsequently, the promoter activities of p21 and p53 were inactivated significantly. However, BMI-1 overexpression noticeably increased Bcl-2 and NF-κB activities. In addition, BMI-1 activated the PI3K/mTOR/4E-BP1 signaling pathways, and sMEK1 significantly inhibited BMI-1-stimulated oncogenesis. These insights provide evidence that BMI-1 activates cell growth and suppresses apoptosis. Collectively, our data indicate that BMI-1 plays a pivotal role in the progression of ovarian cancer, thus representing a novel target for antitumor therapy of ovarian cancer.

Original languageEnglish
Pages (from-to)579-586
Number of pages8
JournalOncology Reports
Volume37
Issue number1
DOIs
StatePublished - Jan 2017

Keywords

  • BMI-1
  • Ovarian tumor metastasis
  • Pro-apoptotic activity
  • Protein-protein interaction
  • sMEK1

Fingerprint

Dive into the research topics of 'BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death'. Together they form a unique fingerprint.

Cite this