Articles in 2015

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.

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.

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.

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.

Compared with most intracellular vesicles, the autophagosome is formed by an unusual event of vesicle budding involving an elusive sequence of membrane expansions that ends with a double membrane vesicle. It is now shown that actin polymerization inside the forming autophagosome is a driving force for the expansion and assembly of a functional autophagosome.

A new study suggests that fumarase, a metabolic enzyme normally associated with ATP production in mitochondria, is recruited to sites of DNA damage where it produces fumarate to inhibit histone demethylation and promote repair of DNA double strand breaks.

Microtubule polymerization is initiated by γ-tubulin containing complexes. Petry and Vale discuss factors involved in localizing and activating γ-tubulin at different locations in the cell.

Procopio et al. report that combined loss of p53 and the CSL transcriptional regulator leads to stromal and cancer cell expansion by bypassing the fibroblast senescence caused by CSL deficiency and promoting cancer-associated fibroblast activation.

Anastasiadis and colleagues report the presence of two spatially and functionally distinct E-cadherin-based junctional complexes, which influence cell behaviour either by regulating miRNA processing or by promoting p120 catenin and Src signalling.

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.

By screening 85 deubiquitylation enzymes, Zhang and colleagues identify OTUD3 as an enzyme that upregulates PTEN levels by deubiquitylation and acts as a tumour suppressor in synergy with another PTEN DUB, USP13.

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

By analysing inducible knockout mice, Scherer and colleagues report that the adipogenic transcription factor C/EBPα is dispensable for white adipogenesis in mouse embryos, but not in adults.

Gil and colleagues report that mTOR affects the tumour-related effects of the senescence-associated secretory phenotype (SASP), by inhibiting the translation of the MAPKAPK2 kinase and thereby preventing the ZFP36L1-mediated SASP mRNA decay.

Piccolo and colleagues report that the YAP/TAZ factors form ternary complexes with TEAD and AP-1 factors to drive a transcriptional program that promotes cell proliferation and tumour growth.

Watanabe and colleagues demonstrate that the spindle assembly checkpoint protein Mad1 promotes gliding of misaligned chromosomes towards the cell equator, through an interaction with Cut7, a kinesin-5 motor.

Using light- and electron microscopy, Khodjakov, Mogilner and colleagues find that the shape of the kinetochore undergoes dramatic changes during mitosis. Computational analysis suggests that this facilitates correct chromosome attachment.

Patel et al. report that Drosophila intestinal stem cell tumours are generated by stress- and EGFR-signalling, followed by extrusion of neighbouring enterocytes, enterocytic cytokine expression and paracrine signalling for tumour growth.

Lu and colleagues find that in response to ionizing radiation, DNA-PK phosphorylates fumarase breaks for local generation of fumarate, which in turn enhances DNA-PK recruitment by inhibiting histone H3 demethylation.