Review Articles in 2006

Adipogenesis is a complex process that involves the integration of a network of signalling pathways and transcription factors. Elucidation of this network will help us understand the events that underlie adipocyte development, with implications for the growing burden of metabolic diseases.

Adenosine to inosine (A→I) RNA editing was once thought to affect only selected transcripts by altering the proteins they encode. But, numerous A→I RNA editing sites have recently been discovered in inverted repeats in non-coding regions. Also, A→I RNA editing frequently interacts with RNA-interference pathways.

The concept of membrane-protein topology is at least 30-years old. However, proteome-wide data on topology, increasing numbers of high-resolution structures and detailed studies on individual proteins are now showing us how topology is determined by the amino-acid sequence.

Membrane-trafficking systems are spatially and temporally organized by the cytoskeleton and molecular motors. In the various endocytic and recycling transport events, microtubule-based long-range transport and actin-based short-range transport require the tightly regulated coordination of myosin, kinesin and dynein motors.

The DNA-damage-induced stalling or collapse of a replication fork can cause genomic instability. This can be avoided by repair and replication-restart mechanisms, but recent evidence indicates that the removal of the blocking lesion is not always required for replication to resume.

New technologies are permitting larger scale and more quantitative studies of signalling networks. The large data sets that are obtained from these studies can be analysed by data-driven modelling approaches. These models are now emerging as standard tools for systems-level research in signalling networks.

Protein tyrosine phosphatases can no longer be viewed as passive housekeeping enzymes. It is now becoming apparent that they have important roles in the regulation of signalling responses. So, what are the functions of these enzymes? And how are they regulated?

Technologies are now in place to obtain large amounts of data for systems biology approaches. What are the most suitable technologies for fast, accurate and high-throughput data collection? And following data collection, how should these data be analysed and validated?

Recent studies of the early secretory pathway have analysed cargo selection and transport-carrier formation by components of the endoplasmic-reticulum-associated coat protein complex-II (COPII). Results are indicative of a unifying model of cage and coat function in vesicle and tubule formation as well as fission in endomembrane traffic.

The ARP2/3 complex regulates the initiation of actin polymerization and the organization of filaments into y-branched networks. Recent studies have begun to reveal the role of this complex in diverse cellular processes and its molecular mechanisms of action, as well as its misregulation during disease.

Regression is a method to estimate parameters in mathematical models of biological systems from experimental data. To ensure the validity of a model for a given data set, pre-regression and post-regression diagnostic tests must accompany the process of model fitting.

Auxins are a class of plant hormones that affect various aspects of plant development. Recent studies have identified certain F-box-domain proteins as auxin receptors that control auxin-regulated gene expression through ubiquitin-mediated proteolysis. Other modes of auxin perception and signalling are also thought to exist.

The study of muscular dystrophies has shown that mutant proteins result in perturbations of many cellular components. These findings have revealed important insights for cell biologists, and have also identified unexpected and exciting new approaches for therapy.

Processive DNA polymerases that replicate chromosomes interact with a ring-shaped clamp that encircles DNA and slides along the duplex. The sliding clamp is loaded onto DNA by a clamp-loader complex. Structural and biochemical studies have provided mechanistic insights into the clamp-loading process.

TheINK4b–ARF–INK4a locus encodes three proteins that are implicated in senescence and tumour suppression. Individual genes are controlled by positive and negative regulators in different contexts, and the entire locus might be suppressed by a cis-acting regulatory domain or by Polycomb-group repressors.

The Notch pathway functions during diverse developmental and physiological processes. Our current understanding of the mechanisms that function on the core Notch pathway shows that we are still just beginning to understand the full complexities of Notch regulation.

Homologous recombination has an important role in DNA repair, DNA replication, meiotic chromosome segregation and telomere maintenance. Its tight regulation by DNA helicases and mediator proteins is essential to avoid cell-cycle arrest, genome destabilization and cancer formation.

Since their discovery in the late 1980s, SNARE proteins have been recognized as key components of protein complexes that drive intracellular membrane fusion. Despite considerable sequence divergence, their mechanism seems to be conserved and is adaptable for diverse fusion reactions.

The recent mapping of histone modifications across theSaccharomyces cerevisiaegenome has allowed the analysis of how combinations of modified and unmodified chromatin states relate to each other and particularly to chromosomal landmarks, such as heterochromatin, centromeres, promoters and coding regions.

The anaphase promoting complex/cyclosome (APC/C) is the largest known complex that catalyses ubiquitylation reactions and has key functions in the eukaryotic cell cycle. Recent studies have shed light on how APC/C activity is controlled and how it recognizes a multitude of substrates.