Trends in Cell Biology最新文献

Over the past few years there has been an alarming burst of cancer burden worldwide. Cancer stem cells (CSCs) act as hidden devils within tumors, rendering cancer therapy a strenuous goal. Recently, the ubiquitin proteasome system (UPS) was proved to be an essential contributor to the CSC phenotype. This forum article aims to outline new strategies/technologies targeting UPS modulation in CSCs as a potential novel modality for efficient cancer therapy.

G protein-coupled receptor 75 (GPR75) is emerging as a promising target for obesity treatment, but its exact role in energy regulation remains unclear. This article explores the latest research on GPR75's molecular function, potential ligands, and therapeutic challenges in addressing obesity.

The concept that ribosomes are sensors of translational distress has sparked significant interest, although much of the research has been conducted in vitro. A new study by Vind et al. provides in vivo evidence that the ribotoxic stress response (RSR) serves as the first line of defense against ultraviolet (UV) radiation.

A byproduct of mitochondrial energy production is the generation of reactive oxygen species (ROS). Too much ROS is toxic, but ROS deficiency is equally deleterious (reductive stress). In a recent study, McMinimy et al. uncovered a ubiquitin proteasome-mediated mechanism at the translocase of the outer membrane (TOM) complex, which senses ROS depletion and adjusts mitochondrial protein import accordingly.

Recent studies in yeast reveal an intricate interplay between nuclear envelope (NE) architecture and lipid metabolism, and between lipid signaling and both epigenome and genome integrity. In this review, we highlight the reciprocal connection between lipids and histone modifications, which enable metabolic reprogramming in response to nutrients. The endoplasmic reticulum (ER)-NE regulates the compartmentalization and temporal availability of epigenetic metabolites and its lipid composition also impacts nuclear processes, such as transcriptional silencing and the DNA damage response (DDR). We also discuss recent work providing mechanistic insight into lipid droplet (LD) formation and sterols in the nucleus, and the collective data showing Opi1 as a central factor in both membrane sensing and transcriptional regulation of lipid-chromatin interrelated processes.

The role of the chromatin remodeler HELicase Lymphoid Specific (HELLS) has been historically associated with DNA methylation and DNA damage repair. However, recent studies have shed light on an unexpected, multimodal, and direct participation of HELLS in transcriptional regulation. This forum article aims to discuss how, through different and context-specific mechanisms, HELLS modulates the expression of functionally related genes favoring transcriptional plasticity and phenotypic adaptation, ultimately safeguarding the genome organization and stability.

The dynamic turnover of actin filaments drives the morphogenesis and migration of all eukaryotic cells. This review summarizes recent insights into the molecular mechanisms of actin polymerization and disassembly obtained through high-resolution structures of actin filament assemblies. We first describe how, upon polymerization, actin subunits age within the filament through changes in their associated adenine nucleotide. We then focus on the molecular basis of actin filament growth at the barbed end and how this process is modulated by core regulators such as profilin, formin, and capping protein (CP). Finally, the mechanisms underlying actin filament pointed-end depolymerization through disassembly factors cofilin/cyclase-associated protein (CAP) or DNase I are discussed. These findings contribute to a structural understanding of how actin filament dynamics are regulated in a complex cellular environment.

Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) regulate numerous biological processes through interaction with signaling effectors at the cell surface. As a unique feature, GPI-APs can be released from their anchors by multi-pass GPI-specific phospholipases (types A2, C, and D) to impact signaling networks, phenotype, and cell fate; however, many questions remain outstanding. Here, we discuss and expand our current understanding of the distinct GPI-specific phospholipases, their substrates, effector pathways, and emerging physiological roles, with a focus on the six-transmembrane ecto-phospholipases GDE2 (GDPD5) and GDE3 (GDPD2). We provide structural insight into their AlphaFold-predicted inner workings, revealing how transmembrane (TM) domain plasticity may enable GPI-anchor binding and hydrolysis. Understanding lipolytic cleavage of GPI-APs adds a new dimension to their signaling capabilities and biological functions.

The target of rapamycin complex mTORC1 has key roles in cell growth and metabolism and its inhibition delays ageing. Recent work by Ogawa et al. in Caenorhabditis elegans argues that modulation of pre-mRNA splicing factors and alternative splicing are key mediators of mTORC1 signalling and can enhance longevity.