Open questions in the NF-κB field.

A variety of stress signals leads to activation of the inducible transcription factor NF-κB, one of the master regulators of the innate immune response. Despite a wealth of information available on the NF-κB core components and its control by different activation pathways and negative feedback loops, several levels of complexity hamper our understanding of the system. This has also contributed to the limited success of NF-κB inhibitors in the clinic and explains some of their unexpected effects.

ULK1/2 Restricts the Formation of Inducible SINT-Speckles, Membraneless Organelles Controlling the Threshold of TBK1 Activation.

Membraneless organelles (MLOs) are liquid-like subcellular compartments providing spatiotemporal control to biological processes. This study reveals that cellular stress leads to the incorporation of the adaptor protein SINTBAD (TBKBP1) into membraneless, cytosolic speckles. Determination of the interactome identified >100 proteins forming constitutive and stress-inducible members of an MLO that we termed SINT-speckles.

Differential intracellular localization and dynamic nucleocytoplasmic shuttling of homeodomain-interacting protein kinase family members.

The three canonical members of the family of homeodomain-interacting protein (HIP) kinases fulfill overlapping and distinct roles in cellular stress response pathways. Here we systematically compared all three endogenous HIPKs for their intracellular distribution and mutual interactions. The endogenous HIPKs are contained in high molecular weight complexes of ~700 kDa but do not directly interact physically.