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Our understanding of the downstream effectors and upstream regulators of target of rapamycin (TOR) signalling continues to grow. In particular, recent global 'omics' studies have revealed physiological roles of mammalian TOR (mTOR) in protein, nucleotide and lipid synthesis, and other studies showed that Hippo, WNT and Notch signalling are novel regulators of mTOR.
Intermediate filaments (IFs) are cytoskeletal and nucleoskeletal structures that promote cell integrity and intracellular communication and contribute to subcellular and tissue-specific functions. Our understanding of how post-translational modifications of IF proteins (including nuclear lamins and cytoplasmic keratins, vimentin, desmin, neurofilaments and glial fibrillary acidic protein, among others) regulate IF function is increasing.
Epithelial–mesenchymal transition (EMT) is integral to development and pathology. This switch in cell differentiation and behaviour requires key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix–loop–helix transcription factors, and is regulated by several signalling pathways, including those mediated by the transforming growth factor-β (TGFβ) family.
Endocycling cells successively replicate their genomes without segregating chromosomes during mitosis and thereby become polyploid. Lack of chromosome segregation typically results from downregulation of mitotic cyclin-dependent kinase activity. Endocycles probably evolved many times, and the various endocycle mechanisms found in nature highlight the versatility of the cell cycle control machinery.
Proteome maintenance was thought to be controlled in a cell-autonomous manner. However, recent findings suggest that proteostasis can be systemically regulated. Protein-folding defects systemically activate proteostasis mechanisms through signalling pathways that coordinate stress responses among tissues, and this may also coordinate ageing rates between tissues.