Reviews & Analysis

Tumorigenesis invariably requires multiple hits. New data shows that carcinogenesis originating from Ras mutations also requires increased Ras levels and a block of cellular senescence. Intriguingly, low non-transforming levels of Ras do not trigger senescence, suggesting that this programme is only activated in response to bona fide cancer threats.

Generation of GTP-bound Ran on chromatin by its guanine nucleotide-exchange factor RCC1 provides a spatial signal that controls nuclear-envelope formation, nucleo-cytoplasmic transport and mitotic spindle assembly. A study now identifies an unusual post-translational modification, α-N-methylation of the amino-terminal tail of RCC1, which anchors the protein on chromosomes.

Voltage-dependent anion channels (VDACs) are thought to participate in mitochondrial-membrane permeabilization, an event that frequently delimits the frontier between cell life and death. Recent work casts doubts on their contribution to mitochondrial cell death.

p53 is usually referred to as a commonly altered tumour suppressor gene. A new study supports a decade of accumulating evidence that mutated p53 protein can gain new functions and also behave as an oncogene. This study specifically suggests that certain p53 mutants gain the ability to inhibit the MRN–ATM signalling pathway.

Dendritic cells are specialized antigen-presenting cells. As such, they exhibit limited degradation of phagocytosed antigens, which favours efficient antigen presentation to T lymphocytes. Work now shows that the restricted proteolysis is due to alkalinization of the phagosome through Rab27a-dependent fusion with a subset of lysosomal vesicles bearing NADPH–oxidase complexes.

The detrimental effects of nuclear factor-kappa B (NF-κB) signalling in cancer cells lacking the oestrogen receptor have now become clear, with the demonstration that increased NF-κB levels induce expression of Bcl-2 to both suppress apoptosis and induce epithelial–mesenchymal transitions (EMTs).

Nine inherited neurodegenerative disorders are caused by polyglutamine (polyQ) expansions in diverse proteins. A study now suggests that polyQ-mediated depletion of nonhistone chromatin proteins enhances genotoxic stress induced by the disease protein.

In mammalian cells, DNA double-strand breaks (DSBs) are repaired by the non-homologous end-joining (NHEJ) pathway. A key component of this repair mechanism is the DNA binding protein, Ku. A recent study shows that Par-3, a protein involved in cell polarity and the assembly of tight junctions, interacts with Ku and is involved in NHEJ, suggesting an intriguing new role for Par-3 and links between cell morphology and DNA damage response pathways.

Viral transmission from an infected cell to a target cell has been long appreciated to be more efficient than infection with a cell-free virus. New work using high-resolution, live-cell microscopy techniques provides important insights into the mechanisms underlying the efficiency of retrovirus transmission between cells.

Lymphocyte migration is activated in response to inflammation and largely depends on the modulation of actin dynamics, and remodelling of the cytoskeleton, following cytokine stimulation. A novel pathway modulating inflammatory-cell migration in vivo that involves the unlikeliest of partners, the inflammatory caspase-11 and Aip1 (an activator of cofilin-mediated actin depolymerization), has been identified.

Mitogen-activated protein kinase (MAPK) cascades process myriads of stimuli, generating receptor-specific cellular outcomes. New work exploits emergent mathematics of network inference to reveal distinct feedback designs of the RAF–MEK–ERK cascade induced by two different growth factors. The study shows that response specificity can arise from differential signal-induced wiring of overlapping protein networks.

Although the molecular machinery controlling aging has been well studied in lower organisms, it is unclear whether these mechanisms are conserved in mammals. A recent study supports a role for an evolutionarily conserved transcriptional pathway in maintaining the unlimited lifespan of haematopoietic stem cells.

Despite being largely a post-mitotic tissue, adult skeletal muscle exhibits a remarkable capacity for regeneration. A new study has shown that cells derived from mural cells (pericytes) from blood vessels in postnatal human skeletal muscle contribute to robust skeletal muscle regeneration after intra-arterial delivery into a dystrophic mouse model.

The microtubule associated protein tau is involved in the neuropathology of Alzheimer's disease, however, the mechanistic basis for the involvement of tau is unclear. New evidence indicates that tau may mediate neurotoxicity by altering the organization and dynamics of the actin cytoskeleton.

The transcription factor GATA-3 is necessary for the formation of a mammary gland and the maintenance of mammary-cell differentiation. The loss of GATA-3 function in a fully formed mammary gland generates oestrogen receptor-negative, proliferating cells that lack expression of myoepithelial markers. Cells with similar characteristics in breast cancer are associated with poor prognosis.

In proliferating cells, the SCF^Skp2ubiquitin ligase targets the CDK inhibitor p27 for proteolysis. A study now shows that the tumour suppressor pRb promotes the APC/C^Cdh1–mediated degradation of Skp2, resulting in the accumulation of p27.

The Ringberg Colloquium on Self-Organization and Morphogenesis in Biological Systems took place between December 3–6, 2006 in a castle near Munich, Germany. Researchers from different areas of cell and developmental biology exchanged ideas about how biological systems are organized and dynamic at the same time. A dominant theme was that local interactions between molecules or cells can generate global order.