Reviews & Analysis

The anaphase-promoting complex (APC) mediates the ubiquitination and degradation of key M-phase regulators, including cyclins and the anaphase inhibitor securin. Intriguingly, securin can also inhibit the degradation of cyclin B. This competition between substrates permits the accumulation of enough cyclin to drive entry into M phase.

Kinetochores maintain a mechanical grip on disassembling microtubule plus ends, possibly through a 16-member Dam1 ring that acts as a sliding clamp. It turns out, however, that a ring is not required for maintaining grip: individual Dam1 complexes in vitro can diffuse on the microtubule lattice and track shortening microtubule tips.

How cells decide that a protein is misfolded is a mystery. The endoplasmic reticulum integrates N-linked glycosylation into the decision as to whether a protein is misfolded. The basic strategy of glycan-based recognition, previously identified in yeast, is conserved in mammals but is expanded, possibly to accommodate a more complex client portfolio.

The cell adhesion molecule TAG1 has been identified as the ligand that induces β-amyloid precursor protein (APP) processing and signalling, resulting in the inhibition of neurogenesis. These findings demonstrate a critical role of TAG1–APP signalling in brain development and suggest the potential involvement of TAG1 in adult neuroplasticity and pathogenesis of Alzheimer's disease.

Hypoxia is a critical factor during tumour progression, regulating the expression of multiple factors implicated in tumour growth, epithelial to mesenchymal transition (EMT) and invasive cell behaviour. We now learn that the EMT inducer Twist operates under the control of hypoxia signalling in the tumour microenvironment.

Newly formed centrioles can spring forth from clouds of pericentriolar material, violating the precise regulation of centriole counting. These observations challenge the long-standing view that centriole number is determined by the periodic activation of an assembly template thought to reside on pre-existing centrioles.

Two studies report expression of telomeric-repeat-containing RNAs in vertebrates. This discovery challenges the long-standing notion that telomeres are transcriptionally inert.

Nerve growth factor induces sensory neuron survival via retrograde signalling from the axon to the cell body. Local translation of the transcription factor CREB in the axon, followed by its transport to the nucleus, is involved in this process.

Constitutively active ERK signalling stimulates cell proliferation, thereby contributing to tumorigenesis. We now learn that ERK activity induces phosphorylation and MDM2-mediated degradation of the tumour-suppressing transcription factor FOXO3a, thus gaining new information on valuable targets for human cancer therapeutic intervention.

Most chloroplast proteins are encoded in the cell nucleus, translated in the cytosol, and targeted to the organelle in a post-translational manner. Our understanding of how proteins are targeted to the outer envelope membrane of chloroplasts has been improved with the identification of a specific soluble sorting factor.

Ena/VASP family members have a common binding interface on their EVH1 domains for FPPPP motifs in partner proteins. The finding that Tes, a protein lacking FPPPP motifs, competes specifically for the FPPPP ligand site on Mena, provides new insights into the differential regulation of Ena/VASP proteins.

Planarian flatworms regenerate their heads and tails after amputation. It turns out that they use Wnt–β-catenin signalling to determine where the head and the tail should form.

Two studies suggest that the primary cilium, a microtubule-based structure protruding from the surface of most vertebrate cells, has a role in restraining Wnt/β-catenin signalling. These findings have implications for the pathogenesis of a plethora of diseases associated with abnormal cilia; however, the mechanism linking Wnt signalling and cilia remains a mystery.

Spir proteins nucleate actin polymerization by assembling a linear actin oligomer along a cluster of four actin-binding WH2 domains, and this process is enhanced by formins of the Cappuccino family. The discovery of Spir-like proteins in bacteria indicates that pathogens have adopted this mechanism to manipulate the host actin cytoskeleton.

The spatial and temporal regulation of motor-based transport is essential to ensure precise cargo delivery in all cell types. New light has been shed on mechanisms controlling cargo–motor interactions, with the finding that NMDA-cargo is released from KIF17 kinesin following motor phosphorylation by CaMKII near the synapse.

Covalent modifications of histone tails are highly correlated with different states of gene expression. Although the biological significance of many such modifications has been elucidated, the physiological role of Thr 11 phosphorylation on histone H3 (H3T11) has remained elusive.

Successful animal cloning after nuclear transfer requires efficient reprogramming to achieve totipotency. Erasure of pre-existing marks is not always efficient and some genes can escape reprogramming and maintain their original active transcriptional state. Ng and Gurdon propose that the histone H3.3 variant is a key player in this process.

How viruses manage to resist physical and chemical stress and yet open their protective coats during cell infection has been a longstanding, fundamental question. A study with the DNA tumour virus SV40 now shows that protein folding and quality-control factors of the endoplasmic reticulum reshuffle disulfide bonds within the viral capsid, providing a molecular mechanism for the exit of infectious virions from the endoplasmic reticulum.

When cancers spread, they detach from their neighbouring cells and invade the surrounding tissues to reach blood or lymphatic vessels. EGF receptors induce cancer invasion by directly activating GEP100, one of several potential activators of the GTP-binding protein Arf6.