The kinase NEK6 positively regulates LSD1 activity and accumulation in local chromatin sub-compartments.

LSD1 plays a crucial role in mammalian biology, regulated through interactions with coregulators and post-translational modifications. Here we show that the kinase NEK6 stimulates LSD1 activity in cells and observe a strong colocalization of NEK6 and LSD1 at distinct chromatin sub-compartments (CSCs). We demonstrate that LSD1 is a substrate for NEK6 phosphorylation at the N-terminal intrinsically disordered region (IDR) of LSD1, which shows phase separation behavior in vitro and in cells.

Pericyclic Cascade Reactions Affording Thienyl- and Benzo[]thienyl-Fused Architectures: A Synthetic and Density Functional Theory Analysis of Asynchronous Diels-Alder Reactions of Thioarylmaleimides.

Herein, we report the synthesis and characterization of a series of thioarylmaleimides and their varied propensity toward highly selective domino Diels-Alder (D-A)/rearrangement, D-A/ene/elimination, and D-A/oxidation reactions to give three types of thienyl-fused architectures. Stereochemical assignment was achieved using a combination of nuclear magnetic resonance (NMR) studies, gauge independent atomic orbital (GIAO) NMR chemical shift calculations, and DP4+ analysis. Transition-state calculations support an asynchronous concerted mechanism and provide support for rationalizing the observed regio- and stereoselectivity.

PKD autoinhibition in regulates activation loop autophosphorylation in .

Phosphorylation is a ubiquitous mechanism by which signals are transduced in cells. Protein kinases, enzymes that catalyze the phosphotransfer reaction are, themselves, often regulated by phosphorylation. Paradoxically, however, a substantial fraction of more than 500 human protein kinases are capable of catalyzing their own activation loop phosphorylation.

Golgi screen identifies the RhoGEF Solo as a novel regulator of RhoB and endocytic transport.

The control of intracellular membrane trafficking by Rho GTPases is central to cellular homeostasis. How specific guanine nucleotide exchange factors and GTPase-activating proteins locally balance GTPase activation in this process is nevertheless largely unclear. By performing a microscopy-based RNAi screen, we here identify the RhoGEF protein Solo as a functional counterplayer of DLC3, a RhoGAP protein with established roles in membrane trafficking.

Optimization of Mechanosensitive Cross-Talk between Matrix Stiffness and Protein Density: Independent Matrix Properties Regulate Spreading Dynamics of Myocytes.

Cells actively sense differences in topology, matrix elasticity and protein composition of the extracellular microenvironment and adapt their function and morphology. In this study, we focus on the cross-talk between matrix stiffness and protein coating density that regulates morphology and proliferation dynamics of single myocytes. For this, C2C12 myocytes were monitored on L-DOPA functionalized hydrogels of 22 different elasticity and fibronectin density compositions.