News & Views in 2006

The BCL-2 oncogene promotes cancer progression by prohibiting cell death. BCL-2-related regulators were once thought to constitute a simple, two-class system of anti-death and pro-death factors. New data delineate a multistep hierarchy of BCL-2-family protein interactions that are driven by signal-dependent pathways.

Primary tumours release soluble factors, including VEGF-A, TGFβ and TNFα, which induce expression of the chemokines S100A8 and S100A9 in the myeloid and endothelial cells within the lung before tumour metastasis. These chemokine-activated premetastatic niches support adhesion and invasion of disseminating malignant cells, thereby establishing a fertile habitat for metastatic tumours.

A new study has revealed an unexpected role for eukaryotic translation initiation factor 4A (eIF4A) in suppressing Decapentaplegic (Dpp) signalling. On activation of Dpp signalling, eIF4A promotes degradation of the downstream signalling components Mad and Medea in a translation-independent manner.

The response of some G-protein coupled receptors (GPRCs) is affected by the voltage across the membrane in which they sit. A study now shows that gating currents, similar to those of ion channels, are associated with this alteration in GPRC activity. The currents depend on structural elements of the receptor that functionally couple to G proteins.

Senescence is an important mechanism for suppressing mammalian tumours and it may also contribute to aging. A new study suggests that changes in the metabolism of oxygen radicals are important for establishing senescence and blocking cytokinesis to ensure senescent cells never divide again.

A new study has identified a novel phospholipase D (PLD) that is located in the mitochondrial outer membrane and is required for organelle fusion. As PLD-catalysed production of fusogenic lipids is critical for many examples of membrane fusion (such as those mediated by SNAREs), this startling finding raises the possibility that mitochondria use a mechanism common to other cellular fusion events.

Loss of tissue organization, including disruption of epithelial polarity, is a feature of many carcinomas. Activation of the oncogenic receptor tyrosine kinase, ErbB2, induces alterations in epithelial architecture, but the mechanisms underlying this effect are poorly understood. New data suggests that the polarity proteins, Par6 and atypical PKC, may affect epithelial polarity and cell survival through interactions with an ErbB2 receptor complex.

Ubiquitin receptors that bind ubiquitinated proteins through ubiquitin-binding domains have key roles in various cellular processes. These receptors are often themselves monoubiquitinated, referred to as coupled monoubiquitination. Now, coupled monoubiquitination has been shown to involve monoubiquitination of a ubiquitin ligase and its subsequent interaction with a ubiquitin receptor.

Correct organization of a polarised microtubule array is vital for eukaryotic cells. Microtubule organizing centers (MTOCs) are generally believed to have an essential role in this process. However, two papers published in this issue have demonstrated that in fission yeast, interphase microtubules can self-organize in anucleate cells lacking any authentic MTOC.

The forkhead box O (FOXO) family of transcription factors regulate cell stress, cell cycle and cell death pathways. Their activities can be modulated by multiple posttranslational modifications, including phosphorylation and acetylation. A recent study adds a new twist to FOXO regulation, showing that coupled ubiquitination and deubiquitination of FOXO may be important for cellular responses to oxidative stress.

Atg5 has been previously characterized as a protein specifically required for autophagy, a lysosomal catabolic pathway for proteins and organelles. However, it has now been shown that, in addition to its role in the formation of autophagosomes, an Atg5 fragment produced by calpain cleavage has pro-apoptotic properties.

A functional bipolar spindle is indispensible for the accurate segregation of chromosomes at mitosis. The centrosomal protein and polo-like kinase-1 (Plk1) substrate Kizuna (Kiz), has now been shown to have a novel function in maintaining spindle-pole integrity and spindle bipolarity.

Understanding how self-renewal and pluripotency — two key characteristics of stem cells — are controlled may allow generation of stem cell lines from somatic tissues, thus avoiding the ethically contentious need to derive them from embryos. A step forward in this understanding was recently taken by two teams, who exploited recombinant retroviruses in gain-and-loss of function experiments to characterize candidate transcription factors with the potential to regulate 'stemness'.

During anaphase, the cysteine protease separase cleaves cohesin and releases sister chromatids. In budding yeast, separase also has a crucial non-proteolytic role in triggering mitotic exit. Separase performs a similar non-catalytic function in frog and mouse oocytes through its physical interaction with cdk1. Vertebrate separase is therefore essential not only for homologue disjunction, but also for bringing about the end of meiosis I.

A new study shows that alveolar macrophages use the cystic fibrosis transmembrane-conductance regulator (CFTR) to maintain lysosomes at low pH and to restrict the growth of ingested bacteria. This may help to explain the persistent infections and chronic inflammation of the lungs that characterize cystic fibrosis.

Cell division in eukaryotes involves a complex self-organization process that drives the transient assembly of dynamic microtubules into a bipolar spindle around the chromosomes to segregate them to the two daughter cells. Spindle shape and size do not depend on the initial spatial organization of the chromatin, but are determined by microtubule motor activities.