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The localization of mRNAs coupled with precise translational control is an important mechanism that is used by cells to establish functionally distinct compartments. Translation of localizing mRNAs is repressed by mechanisms that target translation initiation, and is derepressed following arrival at the final destination.
Transcribed genes are scanned by RNA polymerases, which can detect DNA damage and initiate the transcription-coupled repair (TCR) pathway. Understanding the clinical features and genetic deficiencies of human hereditary diseases that exhibit TCR defects will help to elucidate the mechanism of TCR in eukaryotes.
The quality control process ERAD, endoplasmic reticulum (ER)-associated degradation, results in the removal of aberrant secreted proteins from the ER. Molecular chaperones and associated factors recognize and target substrates for retrotranslocation to the cytoplasm, where they are degraded by the ubiquitin–proteasome machinery.
Recent advances in fluorescent probe technology have improved spatial and temporal resolution, bringing us closer to the ideal of imaging individual cellular features in real time with molecular (1–5 nm) resolution. In parallel, the development of super-resolution imaging techniques has revolutionized fluorescence microscopy.
Conserved proteins of the partitioning defective (PAR), Scribble and Crumbs complexes guide the establishment of cell polarity in various organisms. Small GTPases have also been implicated in cell polarization. How do the polarity complexes and the small GTPases coordinate cellular polarization in different cell types?
Tissue structures and shapes can be formed by organizing groups of cells into different polarized arrangements and by coordinating their polarity in space and time. Conserved design principles that underlie tissue polarity are emerging from studies of model organisms and tissues.
Polarization requires the coordinated interaction of three machineries that modify the basic mechanisms of intracellular protein trafficking and distribution. The integration of these mechanisms into a complex and dynamic network is crucial for normal tissue function and is often defective in disease states.
Actin and microtubules are dynamic polar polymers that are well suited for providing the structural basis for cell polarity. The actin cytoskeleton generally drives symmetry breaking, whereas microtubules control polarity maintenance. These events are coordinated by bidirectional crosstalk between actin and microtubules.
The positioning of each cytoskeletal or membrane organelle must be coupled to that of other organelles in order to contribute efficiently to cell polarity. The non-random positioning of organelles is preserved and transmitted through cell division.
Biochemical oscillations are generated by complex interactions between genes, proteins and cellular metabolites and underlie many processes. Oscillatory behaviour is characterized by negative feedback with time delay, nonlinearity of the reaction kinetics and proper balancing of the timescales of opposing chemical reactions.
The RSK proteins are downstream effectors of the Ras–MAPK signalling cascade. Significant advances in RSK and Ras–MAPK signal transduction expand the current models of RSK-mediated signalling and highlight important functions for RSK proteins in cell survival, growth, proliferation and migration.
Phagosome maturation is the process by which a particle-containing phagosome 'matures' through a series of increasingly acidic membrane-bound structures, becoming an acidic phagolysosome before fusing with lysosomes. The identification of a pathway for apoptotic cell-containing phagosomes reveals parallels and differences with receptor-mediated endocytosis.
Ataxia-telangiectasia (A-T) was first described over 80 years ago. Since the discovery of the A-T mutated (ATM) protein, which is defective in A-T, rapid progress has been made regarding how ATM functions together with many other proteins to protect against genome instability.
Gene regulatory networks control many cellular processes such as cell cycle, cell differentiation, metabolism and signal transduction. Computational methods, both for supporting the development of network models and for the analysis of their functionality, have already proved to be a valuable research tool.
For more than a century, scientists have observed cells internalized inside other cells. These cell-in-cell structures often consist of viable rather than apoptotic cells, and can form by the invasion of one cell into another, rather than by engulfment. This review will address how cell-in-cell structures might form and what physiological roles they might have.
The retinoblastoma tumour suppressor pRB, the E2F transcription factor and related proteins are conserved in many species of plants and animals. Genetic and biochemical experiments now show that pRB and E2F proteins of worms, flies and mammals share similar core activities and regulatory mechanisms.
The roles of Rho GTPases have been extensively studied in several mammalian cell types using different mutants. The availability of knockout mice for several members of the Rho family is now revealing new information about their roles in signalling to the cytoskeleton and in development.
The tumour suppressor p53 integrates incoming stress signals to prevent malignant progression by inducing cell responses such as apoptosis and senescence. The specific response, coordinated by p53 post-translational modifications and the availability of p53 cofactors, determines the appropriate cellular fate.
A degradation signal (degron) is a minimal element that is sufficient for the recognition and subsequent degradation of a protein by the proteolytic machinery. Combined structural and functional studies of degrons are essential for understanding how the ubiquitin–proteasome system is usedin vivo.
Nectins and nectin-like molecules (Necls) are transmembrane cell adhesion molecules that have recently been shown to have a variety of cellular functions. They have roles in cell–cell adhesion, differentiation, polarization and survival, as well as in contact inhibition of cell movement and proliferation.