MK3 controls Polycomb target gene expression via negative feedback on ERK

MK3 Modulation Affects BMI1-Dependent and Independent Cell Cycle Check-Points

Although the MK3 gene was originally found deleted in some cancers, it is highly expressed in others. The relevance of MK3 for oncogenesis is currently not clear. We recently reported that MK3 controls ERK activity via a negative feedback mechanism. This prompted us to investigate a potential role for MK3 in cell proliferation. We here show that overexpression of MK3 induces a proliferative arr...

Cutting Edge: Polycomb Gene Expression

A positive feedback loop regulates the expression of polycomb group protein BMI1 via WNT signaling pathway.

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-bo...

Genome-wide polycomb target gene prediction in Drosophila melanogaster

As key epigenetic regulators, polycomb group (PcG) proteins are responsible for the control of cell proliferation and differentiation as well as stem cell pluripotency and self-renewal. Aberrant epigenetic modification by PcG is strongly correlated with the severity and invasiveness of many types of cancers. Unfortunately, the molecular mechanism of PcG-mediated epigenetic regulation remained e...

A negative feedback loop controls NMDA receptor function in cortical interneurons via neuregulin 2/ErbB4 signalling

The neuregulin receptor ErbB4 is an important modulator of GABAergic interneurons and neural network synchronization. However, little is known about the endogenous ligands that engage ErbB4, the neural processes that activate them or their direct downstream targets. Here we demonstrate, in cultured neurons and in acute slices, that the NMDA receptor is both effector and target of neuregulin 2 (...