Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
YAP and TAZ are transcription coactivators with key roles in development and regeneration as well as in cancer. Many of these roles are executed by YAP/TAZ activation in stem cells. This Review discusses how YAP/TAZ regulate stem cell biology, and considers potential applications of modulating YAP/TAZ in regenerative medicine and cancer therapy.
Mechanistic target of rapamycin mTOR complex 1 (mTORC1) is a central regulator of cellular metabolism. Recent studies of the molecular architecture of mTORC1 shed new light on its physiological functions and on the consequences of their dysregulation in cancer, type 2 diabetes and neurodegeneration.
The transforming growth factor-β (TGFβ) family of cytokines act in development and in homeostasis to regulate cell fate decisions. New insights reveal that small perturbations in TGFβ signalling are tolerated during early development but lead to cancer or congenital disorders at later stages.
The receptor-interacting serine/threonine-protein kinase 1 functions as a molecular switch to control cell survival, inflammation and cell death. Recent mechanistic studies shed light on the catalytic and non-catalytic roles and on the context-dependent functions of receptor-interacting serine/threonine-protein kinase 1 in health and disease.
Endoplasmic reticulum-associated protein degradation (ERAD) enables removal of aberrant or surplus proteins from the ER. ERAD represents a collection of independent processes exhibiting distinct yet overlapping selectivity for a wide range of substrates, enabling efficient quality control of membrane and secretory proteins.
Heat shock protein 90 (HSP90) is a chaperone that facilitates protein folding. In diseased cells, HSP90 and its co-chaperones form oligomers, known as epichaperomes, that confer aberrant scaffolding and holding functions onto the chaperone.
Vascular endothelial growth factor A (VEGFA) is an important regulator of angiogenesis. Increasing knowledge of its role in pathophysiology has culminated in the wide use of anti-VEGFA agents in oncology and in the treatment of neovascular eye disorders, and has opened avenues for promoting tissue vascularization in regenerative medicine.
All aspects of gene regulation involve RNA helicases, which bind or remodel RNA and RNA–protein complexes. Recent data establish a link between helicase structure, mechanism of function and biological roles, including in diseases such as cancer and neurological disorders, with implications for the design of small-molecule inhibitors.
BCL-2 proteins fulfil important functions in cell death as initiators, guardians and executioners of mitochondrial outer membrane permeabilization. Recent findings demonstrating complex interactions among BCL-2 proteins set forth a comprehensive model of BCL-2 action.
Nucleobase modifications are prevalent in eukaryotic mRNA and are broadly required for post-transcriptional gene regulation. The most studied mRNA modification is N6-methyladenosine (m6A), yet various other modifications are now being identified and studied. This Review discusses the emerging mechanisms and roles of these non-m6A modifications.
Single-cell multi-omics methods are essential for characterizing cell states and types. The past decade has ushered in improvements in spatial resolution and computational data integration and in new omics modalities. Consequently, single-cell multi-omics have advanced fundamental and translational research, including, for example, in production of cell atlases and in tumour immunology therapeutics.
Actin is most frequently associated with cell migration and shape control. However, actin has a multitude of other cellular roles, including regulating the function and dynamics of organelles. This Review discusses a plethora of actin functions in mitochondrial biology.
Structural maintenance of chromosomes (SMC) complexes, which connect regulatory DNA elements, form chromatin loops and hold together sister chromatids, are required for accurate chromosome segregation and of control transcription, replication and DNA repair. It has recently become clear that SMC complexes also control nuclear organization by counteracting clustering between similar chromatin regions.
Skeletal muscles show high metabolic flexibility and functional plasticity in their response to different exercise modalities. Recent findings have advanced our understanding of signalling, transcriptional and epigenetic mechanisms that regulate muscle adaptation to exercise and their impact on muscle physiology.
Phospholipids are asymmetrically distributed between membrane leaflets but change their location in various biological processes, which requires designated proteins — flippases and scramblases. Recent insights into the functional mechanisms of these proteins pave the way for better understanding of the roles of membrane asymmetry and the (patho)physiological consequences of its disruption.
Spindle assembly during cell division requires self-organization of microtubules into a complex, bipolar structure that directs the movement of chromosomes. Recent advances reveal the emergent properties of the spindle, most importantly its mechanical features, that facilitate robust assembly and chromosome segregation.
The spindle assembly checkpoint (SAC) ensures correct chromosome segregation during mitosis by inhibiting anaphase until all kinetochores are attached to microtubules. Recent studies highlight the dynamic properties of SAC signalling and begin to explain signal integration at mammalian kinetochores, which feature multiple attachment points.
Despite the crucial roles of Hedgehog signalling in development and tissue regeneration, aspects of the Hedgehog signalling mechanism have been uncovered only recently. These studies reveal a central role for lipids in the Hedgehog signal activity, and provide new insights into the therapeutic potential of modulating Hedgehog signalling in tissue regeneration.
Pools of quiescent adult stem cells support tissue turnover and regeneration in mammals. Recent studies shed new light on the roles of post-transcriptional mechanisms in controlling entry into, maintenance of and exit from the quiescent state, with important implications for regenerative medicine.
