Reviews & Analysis

A feature of the cell cycle is that the events of one cycle must be reset before the next one begins. A study now shows that the replication machinery is removed from fully replicated DNA by a conserved ubiquitin- and CDC48 (also known as p97)-dependent pathway. This explains how eukaryotic chromosomes are returned to the unreplicated state.

The role of the epithelial-to-mesenchymal transition in tumour progression remains a topic of intense debate. Now, data on the role of Zeb1 in the metastatic spread of pancreatic cancer clarify apparently conflicting views by revealing context-specific, differential use of individual epithelial-to-mesenchymal transition transcription factors in cancer cell dissemination.

The metabolic transition from mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis is critical for somatic reprogramming of induced pluripotent stem cells (iPSCs). SIRT2 has now been established as a previously unknown regulator of this metabolic transition during somatic reprogramming by controlling the acetylation status of glycolytic enzymes.

The non-essential amino acids serine and glycine are critical for proliferative metabolism. A study in Nature now finds that dietary serine and glycine deprivation inhibits growth of some tumours. Whether this dietary intervention is effective depends on both the oncogenic context and tumour tissue of origin.

The Hippo pathway responds to environmental factors including nutrient availability, cell density and substrate stiffness to regulate organ size. This pathway is now shown to also regulate antiviral defence by modulating the TBK1-mediated control of interferon production.

Although the mitochondrial inner membrane rhomboid peptidase PARL is known to participate in critical signalling cascades, its role in apoptosis has remained unclear. PARL is now shown to process the mitochondrial pro-apoptotic protein Smac (also known as DIABLO) for its subsequent release into the cytosol where it antagonizes XIAP-mediated caspase inhibition to promote apoptosis.

Determining the differentiation potential of stem and progenitor cells is essential for understanding their function, yet our ability to do so is limited by the restrictions of experimental assays. Based on single-cell functional and molecular profiling experiments, a new computational approach shows how lineage commitment may occur in human haematopoiesis.

Genetic mutations in the SHANK family of proteins are linked to multiple neuropsychiatric disorders including autism spectrum disorders. A study now elucidates critical roles for SHANK in regulating integrin-mediated cell–extracellular matrix adhesion, by sequestering integrin activators.

Exposure of mother worms to mild osmotic stress induces gene expression changes in offspring that protect them from strong osmotic stress. Inheritance of protection is now shown to depend on altered insulin-like signalling in the maternal germline, which confers protection through increased expression of zygotic gpdh-2, a rate-limiting enzyme in glycerol biosynthesis.

G1 cyclins are considered essential for DNA replication and cell division. A recent report now shows that some cells can cycle in the absence of G1 cyclins. In embryonic stem cells and cancer cells, G1 cyclins are required to activate cyclin-dependent kinases to phosphorylate core pluripotency factors and maintain pluripotency.

Skeletal muscles are composed of different types of fibres. Can these be thought of as distinct lineages with specific lineage-restricted progenitors? A provocative study now proposes that mesenchymal cells expressing the transcription factor Twist2 act as myogenic progenitors with selective type IIb fibre-differentiation potential.

Tumours are highly complex and contain multiple cell types. Cancer-associated fibroblasts are now shown to have a critical role in directly leading cancer cell invasion. This intercellular interaction relies on a mechanically active cadherin-based junction, and CAF-led invasion is demonstrated to require E-cadherin in the cancer cell.

Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in cancer progression. The previously uncharacterized lncRNA MAYA is now shown to promote bone metastasis by bridging ROR1–HER3 and Hippo–YAP pathways. Neuregulin-induced HER3 phosphorylation by ROR1 recruits a MAYA-containing protein complex to methylate Hippo/MST1 and activate YAP target genes that are essential for bone metastasis.

Under misfolded protein stress, the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) to restore homeostasis, or commits the cell to apoptosis. A study now uncovers how the UPR is governed by the circadian clock to adjust ER protein-folding capacity to metabolic demand and protect against liver damage.

Spectacular images of the process of myosin II filament formation and organization in migrating cells are unveiled by super-resolution imaging. A combination of short- and long-range interactions with actin filaments is seen to play a critical role in filament partitioning and alignment into contractile actin arcs and stress fibres.