Reviews & Analysis

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  • In this issue of Nature Cell Biology, Mercier et al. show that acute changes in membrane tension may be a physiological trigger for ESCRT assembly, which drives membrane scission, luminal vesicle budding, and a wide array of other membrane remodelling events throughout the cell.

    • Robert C. Piper
    News & Views
  • There is increasing appreciation that many proteins self-aggregate in cells to form functional subcompartments, some of which exist as a separate liquid phase. A study now identifies the biophysical properties of AKAP95 protein condensates as critical for supporting cancer cell proliferation and RNA splicing.

    • Bo Liu
    • Omar Abdel-Wahab
    News & Views
  • Secretory proteins undergo multiple rounds of co- and post-translational quality control checks inside the cell, but how their integrity is maintained outside the cell is an emerging topic. A study establishes a model system to investigate how the extracellular proteome is protected and integrates its findings into existing immune pathways.

    • Brant M. Webster
    • Holly K. Gildea
    • Andrew Dillin
    News & Views
  • Cellular senescence has been widely recognised for decades as a stable arrest of cell proliferation. A recent study identifies senescence establishment and maintenance as a dynamic and reversible process regulated by (in)activation of a predetermined enhancer landscape controlled by the pioneer transcription factor AP-1.

    • Sara Zumerle
    • Andrea Alimonti
    News & Views
  • Stem cells tightly link their metabolism to cell fate decisions; however, how cancers co-opt and bypass metabolic pathways for growth advantage remains unclear. New evidence in this issue highlights how cancer stem cells avoid epigenetically driven differentiation by shutting down endogenous serine synthesis and becoming serine auxotrophs.

    • Daniel Haensel
    • Anthony E. Oro
    News & Views
  • The transcription factor oestrogen receptor alpha (ERα) has long been targeted for therapeutic benefit in cancer, but drug resistance can emerge through a multitude of mechanisms. A study now reveals how the ERα cistrome can become reprogrammed to confer resistance to tamoxifen in breast cancer.

    • Xiaoli S. Wu
    • Christopher R. Vakoc
    News & Views
  • CRISPR base editors can induce single-base-pair changes in the genome, although they are often inefficient. A study now shows that fusion of the DNA-binding domain of RAD51 to base editors enhances both the efficiency and the targeting range of optimized enzymes. These ‘hyper-editors’ offer effective tools for disease modeling and gene therapy.

    • Alyna Katti
    • Lukas E. Dow
    News & Views
  • Pluripotent cells generate all types of cells in the body and have largely been classified dichotomously into two types: naïve and primed. Arguing against a binary classification system, a study now discovers a unique transition state between naïve and primed pluripotency and describes the signals that control this transition.

    • Carolyn E. Dundes
    • Kyle M. Loh
    News & Views
  • Active transport along microtubules by molecular motors is a crucial cellular process that is disrupted in human diseases. Single-molecule studies from three independent groups reveal a new molecular mechanism for how cells control the activity of the complex microtubule motor cytoplasmic dynein via the neurodevelopmental protein LIS1.

    • Richard J. McKenney
    News & Views
  • Post-translational histone modifications are important regulators of nuclear reprogramming. A study now reveals that histone lysine demethylase KDM4A-mediated H3K9me3 demethylation in mammalian oocytes is essential for zygotic genome activation and preimplantation development.

    • Julie Brind’Amour
    • Matthew C. Lorincz
    News & Views
  • Groth and colleagues discuss recent advances in chromatin replication and maintenance across mitotic division, with emphasis on replication-coupled chromatin assembly and chromatin maturation post-replication.

    • Kathleen R. Stewart-Morgan
    • Nataliya Petryk
    • Anja Groth
    Review Article
  • YAP and TAZ, paralogous mammalian genes, act as the key transcriptional effectors of the Hippo pathway. Two recent reports show that both YAP and TAZ form liquid–liquid phase-separated bodies that promote gene transcription by engaging in super-enhancers.

    • J. Matthew Franklin
    • Kun-Liang Guan
    News & Views
  • Piwi proteins are aberrantly induced in human tumours, but their function in cancer has been poorly understood. A study now shows that in the absence of piRNA loading, human PIWIL1 promotes pancreatic cancer metastasis by acting as a co-activator of the anaphase-promoting complex/cyclosome (APC/C) to degrade the cell-adhesion protein Pinin.

    • Fan Yao
    • Li Ma
    News & Views
  • The lack of endogenous reporter lines is a bottleneck in the study of subcellular dynamics in human adult stem cell (ASC)-derived organoids. An approach using CRISPR–Cas9-mediated homology-independent organoid transgenesis (CRISPR–HOT) in ASC-derived organoids now narrows the gap between basic research and translational studies in human organoids.

    • Qiutan Yang
    • Koen C. Oost
    • Prisca Liberali
    News & Views
  • Misfolded proteins in the endoplasmic reticulum (ER) are returned to the cytosol and destroyed by a process known as ER-associated degradation (ERAD). Hrd1 has been implicated as the channel that mediates the transport of ERAD substrates to the cytosol. A study demonstrates that Hrd1 is gated by autoubiquitination and a soluble ERAD substrate.

    • Miguel Betegon
    • Jeffrey L. Brodsky
    News & Views
  • Gene editing holds promise for the treatment of cancers that are driven by well-characterised molecular alterations. A study now provides a proof of concept for the feasibility of in vivo gene editing to correct TERT mutations in glioblastoma, providing a platform for the direct manipulation of genetic alterations to reduce tumour growth.

    • Katie Troike
    • Justin D. Lathia
    News & Views
  • Understanding the metabolic rewiring of pancreatic ductal adenocarcinoma is an emerging strategy for identifying cancer-associated liabilities and improving treatment. A new study now elucidates the function of the transaminase BCAT2 in the early stages of tumor development, providing insights that could stimulate novel therapeutic strategies.

    • Mattia Falcone
    • Oliver D. K. Maddocks
    News & Views
  • The ribosome decodes messenger RNAs and constructs proteins based on the genetic blueprint. Ribosomes also associate with non-coding RNAs, such as PIWI-interacting RNA (piRNA) precursors, during the meiotic pachytene stage. Intriguingly, the ribosome mediates pachytene piRNA biogenesis by guiding endonucleolytic cleavage of piRNA precursors.

    • Yuanhui Mao
    • Shu-Bing Qian
    News & Views
  • A mechanism of secretory autophagy explains aspects of the packaging of proteins and RNA into extracellular vesicles and paves the way to a better understanding of their biological roles and medical applications.

    • Janusz Rak
    News & Views