Review Articles in 2007

Histone post-translational modifications have crucial roles in genome management, in part by recruiting specific factors that alter the structural properties of chromatin. These so-called effector complexes often comprise multiple histone-binding modules that may act in concert to regulate chromatin structure and DNA-related activities.

The PML tumour suppressor is necessary for the formation of dynamic nuclear organelles called promyelocytic leukaemia nuclear bodies (PML-NBs). Recent data suggest that different PML-NBs may regulate specific cellular functions according to their protein composition, their position in the nucleus and their mobility.

Given the amino-acid sequence or 3D structure of a protein, how much can we predict about its function using just a desktop computer? The recent explosive growth in the volume of sequence data and advancement in computational methods has put more tools at the biologist's disposal than ever before.

Although integrins and syndecans are crucial for adhesion and multicellular existence, their relative and functional contributions to cell–extracellular matrix interactions remain obscure. However, evidence suggests that synergistic signalling between these adhesion-receptor families is central to their adhesive function, to regulation of cell behaviour and to avoidance of disease.

SUMO (small ubiquitin-related modifier) is a reversible post-translational protein modifier that causes molecular alterations in sumoylated target proteins, leading to changes in localization, activity and stability. In the past 10 years, mechanisms and principles that govern sumoylation have been elucidated.

Transforming growth factor-β (TGFβ)-induced signalling converges on a limited number of SMAD complexes. These complexes effect a plethora of specific and functional responses in both embryos and adult organisms. How are these complex cellular responses elicited?

The successful completion of mitosis requires that late mitotic events occur in a strict sequence. This is regulated, at least in part, by the order in which different cyclin-dependent kinase substrates are dephosphorylated and in which anaphase-promoting complex substrates are degraded.

Cilia — tiny hair-like organelles attached to the cell surface — are located on most polarized cells and have been adapted as versatile tools for various cellular functions. Several molecular mechanisms affecting the structure and function of distinct cilia types are associated with cilia-related disorders.

Phosphorylation is a universal regulatory mechanism that induces changes in protein conformation. However, certain phosphorylated motifs can be further regulated by the prolyl isomerase PIN1, which is of increasing importance in aspects of physiology and disease.

Mitochondria constantly fuse and divide, are actively transported to specific subcellular localizations and have dynamic structures. Mitochondrial dynamics is important for the functional state of mitochondria, and defects can manifest in mammalian development, apoptosis and neurodegenerative disease.

Recent studies of human genetic syndromes and transgenic mouse models with vascular pathology have exposed a crucial function of extracellular control in the regulation of TGFβ bioavailability in the vascular system. This Review discusses such regulation and the implications of defects in this process with regards to human health.

The vacuolar ATPases are proton pumps that have a central role in maintaining the pH of intracellular compartments and in proton transport across the plasma membrane. Their activity is controlled at many different levels and, increasingly, their dysregulation is being linked to specific diseases.

Maintaining the balance between ATP production and consumption is essential for cell survival. AMP-activated protein kinase (AMPK) is an energy sensor that, when energy levels are low, stimulates catabolism to produce ATP and inhibits biosynthesis and proliferation to conserve ATP.

Different classes of RNA molecules are synthesized in the eukaryotic nucleus and are exported through nuclear pore complexes to the cytoplasm by mobile export receptors. Small RNAs follow relatively simple export routes, whereas large RNAs assemble into complex ribonucleoproteins and require specific adaptor proteins.

The chromosomal passenger complex (CPC) orchestrates mitosis and meiosis at several different levels to ensure the accurate distribution of the genetic material to the daughter cells. Its functions range from the regulation of kinetochore–microtubule attachments to sister chromatid cohesion and cytokinesis.

The replication of telomeres poses unique problems, which the cell solves through specific mechanisms that coordinate the synthesis of the leading and lagging strands at telomeres. These mechanisms integrate the conventional replication machinery, telomere maintenance systems, DNA response pathways and chromosomal organization.

Reactive oxygen species (ROS) have been shown to be toxic but also function as signalling molecules. Recent studies have provided insights into the mechanisms that regulate ROS homeostasis and provide specificity in ROS signalling from prokaryotes to mammals.

Recent studies on melanosome formation have provided insights into novel aspects of endosomal sorting that are involved in cell physiology, organelle biogenesis and amyloid formation. Genetic disorders that affect the formation of melanosomes and other lysosome-related organelles are revealing the molecular machinery that controls specialized sorting events.

The relationship between autophagy and apoptosis is complex; autophagy constitutes an adaptive stress response that avoids cell death and suppresses apoptosis under certain circumstances, whereas in other cellular settings it contributes to the demise of cells through an alternative cell-death pathway.

Mutations in genes that regulate endocrine signalling pathways can increase the lifespans of worms, flies and mammals. Endocrine pathways might therefore serve as targets for the manipulation of the ageing process and prevention of age-related diseases.