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.

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.

Peer Reviewed

1

Open Access

1

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