Reviews & Analysis

Protein sumoylation affects many biological processes, but it was not previously thought to target proteins for degradation. Recent findings unravel a new role for small ubiquitin-like modifier (SUMO) as a signal for the recruitment of ubiquitin ligases, which leads to protein ubiquitylation and degradation.

Ubiquitylation targets proteins for degradation or other cellular fates. The HECT enzymes are E3 ubiquitin ligases, which dictate the specificity of ubiquitylation. HECTs regulate trafficking of many receptors, channels, transporters and viral proteins. Their role in metazoans is becoming clearer fromin vivostudies.

Guanine nucleotide-binding (G) proteins are regulated by GTPase-activating proteins and guanine nucleotide-exchange factors. Another class of G proteins is emerging that are regulated by homodimerization. The authors propose that juxtaposition of the G domains of two monomers across the GTP-binding sites activates the biological function of these proteins and the GTPase reaction.

ATP-dependent chromatin-remodelling complexes are well-known regulators of transcriptional processes. Interestingly, the INO80 and SWR1 complexes also participate in a range of pathways that are involved in genome maintenance, such as DNA repair, checkpoint regulation, DNA replication, chromosome segregation and telomere stabilization.

The ubiquitin–26S proteasome system is one of the most pervasive pathways of intracellular protein regulation in plants. It controls hormone signalling, chromatin structure and transcription, tailoring morphogenesis, responses to environmental challenges, self-recognition and the battle between pathogens and their plant hosts.

The journey of the growth cone is similar to a vehicle on a road. Cytoskeletal elements form the 'motor' to move forward and provide traction on the road, whereas a 'navigator' system guides the vehicle to translate environmental signals into directional movement.

The uropod, a protrusion at the rear of amoeboid motile cells such as leukocytes, exemplifies the importance of morphology in cell motility. Although the signalling and structural requirements of uropod formation are being characterized, a clear understanding of uropod function is still lacking.

The attachment of ubiquitin-like proteins (UBLs) to proteins is a central mechanism of modulation of protein function. Enzymatic, structural and genetic studies have elucidated how mechanistically and structurally related E1 enzymes activate UBLs and selectively direct them to downstream pathways.

Ions move across cell membranes through either ion channels or ion pumps. Recently, atomic-resolution structures and high-resolution functional measurements of examples from both channels and pumps have begun to suggest that these molecules need not be as different as was once thought.

Cells have evolved complex mechanisms to control overall protein synthesis and the translation of specific mRNAs. At the heart of this process is the mammalian target of rapamycin (mTOR) signalling pathway, which senses and responds to nutrient availability, energy sufficiency, stress, hormones and mitogens to modulate protein synthesis.

The canonical Wnt pathway controls metazoan development and tissue homeostasis, and its disregulation in humans results in cancer. Transcription of Wnt target genes is regulated by nuclear β-catenin. How does β-catenin interact with chromatin to regulate Wnt target gene transcription?

Polo-like kinases (Plks) are key regulators of cell division that are conserved from yeasts to humans. The functions and regulation of Plks in the cell cycle and in development are being explored in various organisms.

Many proteins must be integrated into or transported across a membrane to reach their site of function. Whereas ATP-dependent factors bind to completed polypeptides and chaperone them until membrane translocation is initiated, a GTP-dependent co-translational pathway couples ongoing protein synthesis to membrane transport.

Coat proteins, such as coat protein I (COPI), couple vesicle formation with cargo sorting to ensure the generation of correctly packaged transport vesicles. Emerging evidence suggests that some long-held views on how COPI vesicles are formed need to be revised.

Endosomes have important roles in processes, including cytokinesis, polarization and migration, in which their function might be distinct from those classically associated with endosomes. We speculate that endosomes function as multifunctional platforms on which unique sets of molecular machines are assembled to suit different cellular roles.

DNA repair occurs in the context of nuclear architecture. Assembly of the repair machinery on damaged chromatin and the ensuing signalling events require tight spatial and temporal coordination. Higher-order chromatin structure, chromatin dynamics and non-random global genome organization also influence genome maintenance.

Epigenetic inheritance concerns the mechanisms that ensure the transmission of epigenetic marks from mother to daughter cell. Chromatin modifications and nuclear organization are candidate epigenetic marks — whether they fulfil the criterion of heritability and what mechanisms ensure their propagation is an area of intensive research.

ATP-binding cassette (ABC) transporters are responsible for the ATP-powered translocation of many substrates across membranes. Structural similarities support a common mechanism by which ABC transporters, both importers and exporters, couple the binding and hydrolysis of ATP to substrate translocation.

The nuclear envelope is a dynamic structure that is disassembled and reassembled during 'open' mitosis in higher eukaryotes. These mitotic changes are subject to both spatial and temporal control mechanisms that are embedded in the more general regulatory network that directs cell division.

Tie receptors and their angiopoietin ligands have important functions during embryonic vessel assembly and maturation, and control adult vascular homeostasis. The structural characteristics and the spatio-temporal regulation of these receptors and ligands provide important insights into their functions.