Light-based control of metabolic flux through assembly of synthetic organelles.

To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems compartmentalize enzymes into organelles or post-translationally induce activity under certain conditions.

The Spatiotemporal Limits of Developmental Erk Signaling.

Animal development is characterized by signaling events that occur at precise locations and times within the embryo, but determining when and where such precision is needed for proper embryogenesis has been a long-standing challenge. Here we address this question for extracellular signal regulated kinase (Erk) signaling, a key developmental patterning cue. We describe an optogenetic system for activating Erk with high spatiotemporal precision in vivo.

Ubiquitin-mediated interaction of p210 BCR/ABL with β-catenin supports disease progression in a murine model for chronic myelogenous leukemia.

We have identified a ubiquitin-binding domain within the NH2-terminal sequences of p210 BCR/ABL and determined that the binding site co-localizes with the binding site for β-catenin. The domain does not support the auto- or trans-kinase activity of p210 BCR/ABL or its ability to interact with GRB2 and activate ERK1/2 signaling. Expression of p210 BCR/ABL, but not a β-catenin-binding mutant, in hematopoietic cells is associated with the accumulation of p-β-catenin (Tyr654) and increased TCF/LEF-mediated transcription.