Document Type
Journal Article
Publication Date
2-1-2013
Journal
Journal of Biological Chemistry
Volume
Volume 288, Issue 5
Inclusive Pages
3406-3418
Keywords
Feedback, Physiological; Gene Expression Regulation; Neoplastic; Polycomb Repressive Complex 1--genetics; Polycomb-Group Proteins--genetics; Wnt Signaling Pathway--genetics
Abstract
Polycomb group protein BMI1 plays an important role in cellular homeostasis by maintaining a balance between proliferation and senescence. It is often overexpressed in cancer cells and is required for self-renewal of stem cells. At present, very little is known about the signaling pathways that regulate the expression of BMI1. Here, we report that BMI1 autoactivates its own promoter via an E-box present in its promoter. We show that BMI1 acts as an activator of the WNT pathway by repressing Dickkopf (DKK) family of WNT inhibitors. BMI1 mediated repression of DKK proteins; in particular, DKK1 led to up-regulation of WNT target c-Myc, which in turn further led to transcriptional autoactivation ofBMI1. Thus, a positive feedback loop connected by the WNT signaling pathway regulates BMI1 expression. This positive feedback loop regulating BMI1 expression may be relevant to the role of BMI1 in promoting cancer and maintaining stem cell phenotype.
APA Citation
Cho, J., Dimri, M., & Dimri, G. P. (2013). A positive feedback loop regulates the expression of polycomb group protein BMI1 via WNT signaling pathway. Journal of Biological Chemistry, 288(5), 3406-3418.
Peer Reviewed
1
Open Access
1
Comments
This research was originally published in Journal of Biological Chemistry. Joon-Ho Cho, Manjari Dimri and Goberdhan P. Dimri. A positive feedback loop regulates the expression of polycomb group protein BMI1 via WNT signaling pathway. Journal of Biological Chemistry. 2013; 288:3406-3418. © the American Society for Biochemistry and Molecular Biology.