Latest Reviews

  • Review Article |

    Phosphoinositide 3-kinases (PI3Ks) are lipid kinases that generate 3-phosphoinositides, which govern cellular signal transduction and membrane trafficking. The PI3K family comprises three classes of enzymes, which include several isoforms and complexes; the myriad of cellular functions and means of regulation of these enzymes are now coming into focus.

    • Benoit Bilanges
    • , York Posor
    •  & Bart Vanhaesebroeck
  • Review Article |

    Nonsense-mediated mRNA decay (NMD) is a quality and quantity control mechanism for degrading mutated mRNAs to protect the integrity of the transcriptome and proteome and unmutated mRNAs to control their quantity. NMD dysfunction in humans is associated with intellectual disability and cancer.

    • Tatsuaki Kurosaki
    • , Maximilian W. Popp
    •  & Lynne E. Maquat
  • Review Article |

    Cellular metabolism is rewired in proliferating cells to support their increased need for macromolecule biosynthesis. A better understanding of how cells utilize nutrients for biosynthetic pathways and how they overcome the metabolic challenges associated with high proliferation rates can lead to better control of cell proliferation and improved cancer treatments.

    • Jiajun Zhu
    •  & Craig B. Thompson
  • Review Article |

    Cilia, and primary cilia in particular, are important signalling organelles with established roles in odorant, light and Hedgehog morphogen signal transduction. Cilia are enriched in signalling receptors and effectors and in specific lipids. Addressing how this unique composition is established and maintained is key to understanding cell signalling.

    • Maxence V. Nachury
    •  & David U. Mick
  • Review Article |

    Components of the ribosome-associated protein quality control (RQC) pathway recognize truncated proteins resulting from the stalling of ribosomes on mRNAs during translation and target them for degradation. Defects in RQC can lead to disease, and recent insights have revealed RQC mechanisms in the cytosol and on mitochondria and the endoplasmic reticulum that involve the E3 ligase listerin and/or the formation of carboxy-terminal alanine and threonine tails.

    • Claudio A. P. Joazeiro
  • Review Article |

    Genome organization can regulate gene expression, but can gene expression regulate genome organization? Recent studies reveal that, although not required for higher-level genome organization, transcription has a role in the formation and stabilization of genomic subdomains and enhancer–promoter interactions.

    • Bas van Steensel
    •  & Eileen E. M. Furlong
  • Review Article |

    Following DNA damage, the transcription factor p53 determines whether cells undergo apoptosis or cell cycle arrest and DNA repair. To enable different cellular outcomes, p53 is regulated through its temporal expression dynamics and post-translational modification, and by interactions with chromatin, chromatin regulators and transcription factors.

    • Antonina Hafner
    • , Martha L. Bulyk
    • , Ashwini Jambhekar
    •  & Galit Lahav
  • Review Article |

    Metabolites can actively regulate biological processes and may directly modulate phenotype. The current challenge of metabolomics is to provide a platform for the discovery of such bioactive metabolites and — in combination with other omics technologies — to determine their biological functions.

    • Markus M. Rinschen
    • , Julijana Ivanisevic
    • , Martin Giera
    •  & Gary Siuzdak
  • Review Article |

    The haematopoietic stem cell (HSC) niche in the bone marrow ensures haematopoiesis by regulating the function of HSCs and progenitor cells. An improved understanding of this regulation in homeostasis, ageing and cancer should aid the development of therapies to rejuvenate aged HSCs or niches and treat malignancies.

    • Sandra Pinho
    •  & Paul S. Frenette
  • Review Article |

    By opposing protein ubiquitylation, deubiquitylating enzymes (DUBs) regulate various cellular processes, including protein degradation, the DNA damage response, cell signalling and autophagy. Many DUBs show high specificity for ubiquitin chain architecture and/or the protein substrate that they recognize, and have emerged as exciting therapeutic targets within the field of proteostasis.

    • Michael J. Clague
    • , Sylvie Urbé
    •  & David Komander
  • Review Article |

    Misfolded proteins have a high propensity to form potentially toxic aggregates. Cells employ a complex network of processes, involving chaperones and proteolytic machineries that ensure proper protein folding and remodel or degrade misfolded species and aggregates. This proteostasis network declines with age, which can be linked to human degenerative diseases.

    • Mark S. Hipp
    • , Prasad Kasturi
    •  & F. Ulrich Hartl
  • Review Article |

    Spatial proteomics improves our understanding of protein function by revealing the subcellular localizations of proteins and their movement between compartments. This Review discusses spatial proteomics approaches, their successful application in cell biology and ways to improve integration of spatial proteomics data.

    • Emma Lundberg
    •  & Georg H. H. Borner
  • Review Article |

    BCL-2 family proteins are the mediators of apoptotic cell death. The balance between pro-apoptotic and pro-survival BCL-2 family members is differently regulated in various physiological contexts to modulate cellular apoptotic susceptibility. Perturbation of this balance causes excessive or insufficient cell death, leading to diseases such as neurodegeneration and cancer.

    • Rumani Singh
    • , Anthony Letai
    •  & Kristopher Sarosiek
  • Review Article |

    Circadian rhythms align organismal functions with phases of rest and activity. Accordingly, circadian oscillations occur in many physiological processes, including various metabolic functions. In turn, metabolic cues are emerging as regulators of the circadian clock. This crosstalk between metabolism and circadian rhythms has important implications for human health.

    • Hans Reinke
    •  & Gad Asher
  • Review Article |

    Recent functional and proteomic studies have revealed the remarkable complexity of mitochondrial protein organization and interactions. This Review discusses how the mitochondrial protein import machinery functions as a key organizer of these protein networks, its involvement in the formation of membrane contact sites, and how defects in protein import can lead to disease.

    • Nikolaus Pfanner
    • , Bettina Warscheid
    •  & Nils Wiedemann
  • Review Article |

    An increase in white adipose tissue is associated with obesity and reduced metabolic function. Interestingly, however, adipose tissue expansion through the generation of new adipocytes (adipogenesis), rather than through increasing adipocyte size, can prevent this metabolic decline. Thus, a better understanding of adipogenesis can inform new strategies to increase metabolic health in humans.

    • Alexandra L. Ghaben
    •  & Philipp E. Scherer
  • Review Article |

    The Hippo pathway effectors YAP and TAZ regulate normal and tumorigenic organ growth. Recent studies in vitro and in mouse models have shown that these two transcription co-activators can also promote tissue regeneration. This property could be exploited for regenerative medicine, as long as the therapeutic approaches can minimize the potential for cancer development.

    • Iván M. Moya
    •  & Georg Halder
  • Review Article |

    Lipid droplets are storage organelles that are important for the regulation of lipid and energy homeostasis, and that serve as buffers against lipotoxicity. Recent studies on the biology of lipid droplets have led to new discoveries about their biogenesis and the complexity of their interactions with other organelles at membrane contact sites.

    • James A. Olzmann
    •  & Pedro Carvalho
  • Review Article |

    Our understanding of eukaryotic ribosome assembly has been boosted by recently published cryo-electron microscopy structures of yeast ribosome assembly intermediates. These studies highlight the roles of RNA compaction, checkpoints and proofreading mechanisms of pre-ribosomal particles in the nucleolus, nucleus and cytoplasm.

    • Sebastian Klinge
    •  & John L. Woolford Jr
  • Review Article |

    Non-histone-lysine acetylation affects protein functions by modulating protein stability, interactions, subcellular localization and enzymatic activity and through crosstalk with other post-translational modifications. Acetylation regulates many cellular processes, such as transcription, DNA repair, signal transduction, protein folding and autophagy.

    • Takeo Narita
    • , Brian T. Weinert
    •  & Chunaram Choudhary
  • Review Article |

    Epithelial–mesenchymal transition (EMT) is crucial for embryogenesis, wound healing and cancer development, and confers greater resistance to cancer therapies. This Review discusses the mechanisms of EMT and its roles in normal and neoplastic tissues, the contribution of cell-intrinsic signals and the microenvironment to inducing EMT, and its effects on the immunobiology of carcinomas.

    • Anushka Dongre
    •  & Robert A. Weinberg
  • Review Article |

    Epigenetic profiling of germline and zygotic genomes has revealed that a fraction of mammalian genomes do not undergo epigenetic reprogramming during early development, highlighting the importance of epigenetic inheritance in animals. Inheritance of histone modifications, tRNA fragments and microRNAs can affect gene regulation in the offspring; however, in mammals, epigenetic inheritance rarely operates beyond two generations.

    • Ksenia Skvortsova
    • , Nicola Iovino
    •  & Ozren Bogdanović
  • Review Article |

    Recent data indicate that various transcription factors and RNA polymerase II bind to mitotic chromatin and that thousands of genes remain transcriptionally active in mitosis, contradicting the view that mitotic cells are transcriptionally silenced. These mechanisms provide mitotic transcriptional memory, which allows re-establishment of cell-type-specific gene expression following division.

    • Katherine C. Palozola
    • , Jonathan Lerner
    •  & Kenneth S. Zaret
  • Review Article |

    The activity of many cell type-specific enhancers is regulated by histone deacetylase 3 (HDAC3), which acts in complex with various nuclear receptor co-repressors. HDAC3 is required for many aspects of mammalian development and physiology, including the metabolism of various organs, neuronal- and haematopoietic stem cell fate and function, lung and bone development and intestinal homeostasis.

    • Matthew J. Emmett
    •  & Mitchell A. Lazar
  • Review Article |

    The distribution of lipids largely depends on their non-vesicular transport by lipid transfer proteins (LTPs). Recent progress in understanding the mechanisms of LTPs, including the appreciation of their widespread activity at membrane contact sites, has provided novel insights into the regulation of lipid trafficking and how it impacts pathophysiology.

    • Louise H. Wong
    • , Alberto T. Gatta
    •  & Tim P. Levine
  • Review Article |

    Actin and microtubules are essential for key cellular processes, including cell polarization, migration and division. Although their cellular roles are distinct, actin and microtubules also extensively influence each other’s dynamics and organization. This crosstalk encompasses multiple mechanisms and involves various crosslinkers, motors and regulatory proteins as well as mechanical cooperation.

    • Marileen Dogterom
    •  & Gijsje H. Koenderink
  • Review Article |

    Cellular stress responses primarily serve to rectify stress-associated damage. However, these responses are also coupled with the generation of various signals that are transmitted to the cellular microenvironments or even across tissues. This communication generally supports the maintenance of systemic homeostasis but can also result in pathology.

    • Lorenzo Galluzzi
    • , Takahiro Yamazaki
    •  & Guido Kroemer
  • Review Article |

    The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. Recent advances in structural biology techniques have provided insight into how amyloid structure may affect the ability of fibrils to spread in a prion-like manner and into their roles in disease.

    • Matthew G. Iadanza
    • , Matthew P. Jackson
    • , Eric W. Hewitt
    • , Neil A. Ranson
    •  & Sheena E. Radford
  • Review Article |

    The cleavage of microRNA (miRNA) precursors by Drosha and Dicer and their loading with Argonaute proteins into RNA-induced silencing complexes are key steps in miRNA biogenesis. Recent studies have clarified the mechanisms of action of these molecular machines and discovered non-canonical miRNA biogenesis pathways.

    • Thomas Treiber
    • , Nora Treiber
    •  & Gunter Meister
  • Review Article |

    Endocytosed membrane proteins can either be degraded in the lysosome or recycled back to the membrane. This decision, which has an impact on protein levels, spatial distribution and function, is controlled by recycling machineries at the endosome that recognize and segregate cargo destined for recycling, thereby preventing its degradation.

    • Peter J. Cullen
    •  & Florian Steinberg
  • Review Article |

    Uptake of Ca2+ ions by mitochondria regulates their functions and serves to buffer Ca2+ concentrations to maintain cellular Ca2+ homeostasis. Better understanding of the mechanisms, regulation and (patho)physiology of mitochondrial Ca2+ influx and efflux offers the possibility to target mitochondrial Ca2+ machineries for therapeutic benefit.

    • Carlotta Giorgi
    • , Saverio Marchi
    •  & Paolo Pinton
  • Review Article |

    MicroRNAs (miRNAs) are key regulators of biological processes. Recent discoveries have expanded our understanding of the control of miRNA function in animals, through alternative processing, miRNA-sequence editing, post-translational modifications of Argonaute proteins, subcellular localization and regulation of miRNA–target interactions.

    • Luca F. R. Gebert
    •  & Ian J. MacRae
  • Review Article |

    G protein-coupled receptors (GPCRs) control a plethora of signalling pathways in various contexts. Importantly, a single GPCR can elicit different responses depending on the bound ligand — a phenomenon known as biased agonism. Increasing molecular and structural understanding of biased agonism offers the possibility of designing improved GPCR-targeting drugs.

    • Denise Wootten
    • , Arthur Christopoulos
    • , Maria Marti-Solano
    • , M. Madan Babu
    •  & Patrick M. Sexton
  • Review Article |

    Metabolomics and lipidomics have enabled the identification of metabolites (such as lipids, amino acids and bile acids) and metabolic pathways that modulate insulin sensitivity both directly and indirectly. Understanding the metabolic adaptations involved in insulin resistance may lead to novel approaches for preventing and treating T2DM.

    • Qin Yang
    • , Archana Vijayakumar
    •  & Barbara B. Kahn
  • Review Article |

    Protein degradation by the proteasome is crucial for the control of many cellular processes, and defects in proteasomal degradation may lead to cancer and neurodegeneration. TOR complex 1 has a key role in regulating proteasome abundance and assembly and in integrating proteasomal activity with autophagy pathways and, more generally, cell physiology.

    • Adrien Rousseau
    •  & Anne Bertolotti
  • Review Article |

    Translation deregulation causes many human diseases, which can be broadly categorized into tRNA or ribosomal dysfunction, and deregulation of the integrated stress response or the mTOR pathway. The complexity of the translation process and its cellular contexts could explain the phenotypic variability of these disorders.

    • Soroush Tahmasebi
    • , Arkady Khoutorsky
    • , Michael B. Mathews
    •  & Nahum Sonenberg
  • Review Article |

    Recent studies in model organisms uncovered prominent links between autophagy and ageing, suggesting that by removing superfluous or damaged cellular content through lysosomal degradation, autophagy supports tissue and organismal fitness and promotes longevity. Thus, autophagy induction could be considered a strategy to extend lifespan.

    • Malene Hansen
    • , David C. Rubinsztein
    •  & David W. Walker
  • Review Article |

    Core promoters of RNA polymerase II enable highly regulated transcription initiation by integrating cues from distal enhancers. The emerging diversity of core promoters defines distinct transcription programmes and can explain the nature and outcome of transcription initiation at gene start sites and at enhancers.

    • Vanja Haberle
    •  & Alexander Stark
  • Review Article |

    Metabolism feeds into gene regulation, allowing adaptation of gene expression to satisfy cellular needs, including in pathological scenarios such as cancer. Metabolism modulates gene expression through metabolites, which serve as cofactors for DNA and histone modifiers, and through metabolic enzymes, which locally regulate chromatin and transcription in the nucleus.

    • Xinjian Li
    • , Gabor Egervari
    • , Yugang Wang
    • , Shelley L. Berger
    •  & Zhimin Lu