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The amount of the BubR1 checkpoint protein declines with age in mouse models, suggesting that it has a role in ageing. Van Deursen and colleagues reveal that expressing a BubR1 transgene in mice reduces tumorigenesis and aneuploidy, and delays ageing-related phenotypes.
Clark and colleagues have characterized the stages during which global epigenetic reprogramming occurs in human primordial germ cells, and delineate the appearance of these changes at 16 days of differentiation.
The Cdc2 (also called Cdk1) kinase is first activated at the centrosome to initiate mitosis in human cells. Hagan and colleagues demonstrate that in fission yeast, Cdc2 and Polo kinase activation at the spindle pole body remotely controls not only mitotic commitment but also ‘new end take off’, the initiation of bipolar growth in G2.
To segregate chromosomes, spindle microtubules must attach to chromosomes through kinetochores, in a process involving several types of microtubule behaviour. Tolic-Norrelykke and colleagues find that fission yeast microtubules rapidly rotate around the spindle poles, and mathematical modelling confirms that this random microtubule movement facilitates kinetochore capture.
The Wnt/planar cell polarity (Wnt/PCP) pathway orients cell division in various developmental contexts including zebrafish gastrulation. Gonzalez-Gaitan and colleagues reveal that, downstream of Wnt/PCP, the anthrax toxin receptor 2a interacts with actin to form a cortical actin cap in dorsal epiblast cells, and acts through RhoA and the formin zDia2 to orient the mitotic spindle.
Cell biologists must decide whether to embrace the maturing field of systems biology. We argue that a fusion of the two is urgently needed to strengthen both fields.
Epithelial cells have an apical–basolateral axis of polarity, which is required for epithelial functions including barrier formation, vectorial ion transport and sensory perception. Here we review what is known about the sorting signals, machineries and pathways that maintain this asymmetry, and how polarity proteins interface with membrane-trafficking pathways to generate membrane domains de novo.It is becoming apparent that membrane traffic does not simply reinforce polarity, but is critical for the generation of cortical epithelial cell asymmetry.
Basal cell carcinoma has been shown to originate from activation of hedgehog signalling in interfollicular epidermal progenitor cells. Analyses of the early steps of basal cell carcinoma formation show that this process requires reprogramming of interfolliclular epidermal cells to an embryonic hair follicle progenitor-like fate, with concomitant Wnt pathway activation.
Regulation of organ size is achieved through the action of the mTOR and Hippo signalling pathways, which control cell proliferation and cell growth in response to extracellular cues. A link between these pathways is revealed by the finding that YAP downregulates PTEN to promote cell growth and tissue hyperplasia.
Brown adipose tissue is intensively researched owing to its role in regulating energy and glucose homeostasis. Its differentiation is controlled through adrenergic-dependent regulation of the transcriptional co-regulator Prdm16. Adrenergic stimulation inhibits expression of miR-133a/b in a Mef2c-dependent manner to abrogate post-transcriptional silencing of Prdm16.
Patterning of Drosophila embryos involves the localization of RNAs to specific places in the oocytes before fertilization. Although both gurken (grk) and bicoid (bcd) mRNA localize to the dorsoanterior of the oocyte, only grk mRNA is translated at this stage. Davis and colleagues find that grk mRNA co-localizes with proteins involved in translation at the periphery of P bodies whereas bcd is enriched into their central region—which the authors show is devoid of ribosomes—where it is translationally repressed.
Lu and colleagues delineate a pathway through which the PKM2 enzyme promotes aerobic glycolysis, known as the Warburg effect, in cancer cells. They show that EGFR-activated ERK phosphorylates PKM2, leading to its accumulation in the nucleus. Nuclear PKM2 subsequently promotes the c-Myc-dependent upregulation of genes involved in the Warburg effect, resulting in tumour growth.
The mitochondrial calcium uniporter (MCU) mediates calcium uptake by mitochondria and thus regulates cellular bioenergetics, but how MCU activity is modulated is not fully understood. Madesh, Foskett and colleagues report that the integral mitochondrial membrane protein MCUR1 (mitochondrial calcium uniporter regulator 1) binds to the MCU and promotes MCU-dependent calcium uptake to control ATP production and autophagy.
