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Cellular senescence is often accompanied by the production of secreted proteins that mediate the diverse effects of senescence on the tissue microenvironment. The mammalian target of rapamycin (mTOR), a master regulator of protein synthesis, is now shown to control the senescence-associated secretory phenotype by modulating gene transcription and mRNA translation and stabilization.
Decreases in endoplasmic reticulum calcium content are sensed by resident STIM proteins, which can activate plasma membrane Orai channels to facilitate Ca2+ entry. The role of STIMATE, a previously unknown component of the store-operated calcium entry complex, has now been identified and defined.
Using single-cell profiling of Nanog and Oct4 protein levels in mouse embryonic stem cells, Schroeder and colleagues show that differences in Nanog levels are not correlated with differences in expression of other pluripotency factors and cell fate.
Lecuit and colleagues use live imaging and laser ablation approaches to show that germ-band extension of the Drosophila embryo is associated with new junction growth, which is dependent on both tissue-level and local forces.
Zhang et al. report that in response to ROS, ATM regulates peroxisome homeostasis through the phosphorylation of PEX5, which is then ubiquitylated and can be recognized by p62 to specifically activate pexophagy.
Chen et al. produced a quadruple knockout of all the known BH3-only proteins in order to characterize their pro-apoptotic functions. They establish that NOXA is a direct activator of BAX/BAK and not merely a sensitizer as previously suggested.
Yap and colleagues report that robustness of RhoA signalling at E-cadherin junctions is achieved through a feedback network that includes myosin II, ROCK1, Rnd3 and p190B RhoGAP.
Through RNAi screens in C. elegans, Ruvkun and colleagues identify signalling pathways that induce detoxification genes following disrupted translation, suggesting translational surveillance of toxins and virulence factors.
Malumbres and colleagues reveal that mitotic arrest is accompanied by reduced mitochondrial mass and oxidative respiration resulting in activation of AMPK and induction of glycolysis to promote cell survival.
SDH inactivation is associated with cancer susceptibility. Cardaci et al. report a metabolic vulnerability in SDH-deficient cells, by showing that they depend on pyruvate carboxylation for the production of aspartate, proliferation and tumour growth.
The TERT promoter is mutated in many cancers. Li et al. show that non-canonical NF-κB signalling and ETS1/2 transcription factors are jointly needed to activate the C250T mutant TERT promoter, leading to telomerase activity and glioblastoma growth.
Through a proteomic analysis of ER–PM junctions, Zhou and colleagues and Wang and colleagues discover that the transmembrane protein STIMATE is a positive regulator of STIM localization and function, thereby stimulating Ca2+ influx.
Lu and colleagues report that the O-GlcNAcylated MIF cytokine binds the extracellular domain of EGFR and prevents EGF-induced EGFR activation. Conversely, EGFR activation leads to MMP13-mediated MIF degradation and EGFR-induced tumorigenesis
Through proteomics, Harper and colleagues identify proteins interacting with UBXD adaptors for the multifunctional AAA-ATPase VCP and reveal a role for UBXN10 in ciliogenesis.
