Journal of Biological Chemistry

For more than a century, the Journal of Biological Chemistry has served as a home for rigorous, mechanistic studies that define our understanding of biological processes. This commitment to molecular and biochemical insight remains the foundation of the journal.

Most organisms rely on 20 DNA-encoded canonical amino acids (AAs) for protein synthesis. However, hundreds of non-canonical amino acids (NCAAs) occur in nature, many of which are plant secondary metabolites. Some NCAAs have been identified as proteinogenic and can mimic canonical AAs in mammalian protein synthesis. The tRNA synthetases responsible for AA recognition have evolved to discriminate a…

Metabolic reprogramming is a hallmark of neuronal repair, yet the roles of glucose metabolism-related enzymes remain poorly understood. To investigate their functions, we employed a sciatic nerve injury model, taking advantage the intrinsic regenerative capacity of peripheral neurons. After sciatic nerve crush injury, dorsal root ganglia exhibited sustained upregulation of several enzymes in the …

During DNA replication, the topoisomerases TOP1 and TOP2 resolve topological stress associated with DNA unwinding. Based on their catalytic activities, TOP1 is believed to relieve positive supercoil ahead of the replication fork, whereas TOP2 primarily removes topological intertwines between sister chromatids behind the replication fork. As the replication fork rotates, these two TOPs are conside…

Immune checkpoint blockade targeting programmed death ligand-1 (PD-L1) has emerged as a cornerstone of cancer immunotherapy, yielding durable responses in subsets of patients across multiple malignancies. However, clinical outcomes remain limited because of incomplete blockade, low tumor immunogenicity, and poor targeting specificity. Here, we report the development of a chondroitin sulfate-modif…

Gastric cancer (GC) is among the most common malignant tumors worldwide. The inhibition of p53 ubiquitination can inhibit the progression of GC. The mechanism through which plasmolipin (PLLP) regulates p53 ubiquitination in GC remains unclear. In this study, the correlation between PLLP expression and the prognosis of GC was analyzed on the basis of data from The Cancer Genome Atlas database, and…

Transfer RNAs (tRNAs) are essential components of the protein synthesis machinery. Their biogenesis is a highly regulated process that involves the incorporation of numerous post-transcriptional chemical modifications, essential for tRNA folding, cellular stability and function. The sequential process by which these modifications are introduced remains poorly characterized. Previous studies have …

The RNA-binding proteins TIAR and TIA1 have been reported to affect beta cell insulin production and viability. The missense E384K TIA1 autosomal dominant mutation is known to cause Welander distal myopathy. The aim of this study was to study the effects of the TIA1 E384K mutation in human insulin-producing EndoC-βH1 cells. The prime editing technique was used to generate EndoC-βH1 cell clones wi…

Proteasomes are large multisubunit protease complexes found in all domains of life, where they execute regulatory and quality control degradation critical for organismal health. The canonical form of the proteasome, known as the 26S proteasome, consists of a 28-subunit barrel-shaped proteolytic core particle (CP) that is capped on its barrel ends by the 19-subunit regulatory particle (RP). The RP…

Molnupiravir, a prodrug of β-D-N⁴-hydroxycytidine (NHC), is an antiviral RNA mutagen that is incorporated by viral RNA-dependent RNA polymerases (RdRp) during replication of viral RNA genomes, ultimately driving target viruses such as SARS-CoV-2 toward lethal mutagenesis. In this study, first, we biochemically tested whether DNA-dependent RNA polymerases (DdRps) including T7 RNA polyme…

The nucleocapsid (N) protein of SARS-CoV-2 is essential for viral replication and transcription, in part through interactions with host proteins. Here, we delineate distinct mechanisms underlying N protein association with human RNA helicases DDX1 and DDX21. Co-immunoprecipitation assays in HEK293 cells modified to express N protein revealed that DDX1 binding requires the N protein serine-arginin…

Fragile histidine triad (FHIT) is a well-known tumor suppressor frequently downregulated in gastric cancer (GC), yet its molecular mechanisms remain insufficiently understood. In this study, we reveal that FHIT expression is significantly reduced during carcinogen-induced malignant transformation of gastric epithelial cells, independent of its diadenosine triphosphate hydrolase activity. Ribosome…

Isoprene, a C5 hydrocarbon emitted by various land plants, serves as a protective molecule under heat stress. The moss Calohypnum plumiforme isoprene synthase (CpISPS) catalyzes isoprene formation from dimethylallyl diphosphate and contains two aromatic residues (Y393 and F615) at the bottom of the active site that restrict the cavity size to accommodate the smaller C5 substrate. Here we show tha…

Curcumin, a natural polyphenolic compound, is widely recognized for its anti-inflammatory, anti-cancer, and antimicrobial properties. Despite its long history of medicinal use, the precise mechanisms underlying its cellular effects remain incompletely understood. In yeast, curcumin has been shown to activate Hog1, a stress-activated protein kinase (SAPK), but the regulatory basis of this activati…

General and regulatory proteolysis in bacteria is executed by a set of ATP-dependent proteases composed of hexameric ring-forming AAA+ proteins and associated peptidase barrels (e.g. ClpP). These AAA+ proteases play crucial roles in stress protection and bacterial virulence. Here, we provide the first biochemical characterization of the potential drug target ClpE/ClpP from Enterococcus faecalis. …

The Breast cancer susceptibility gene 1 (BRCA1)/BRCA1-associated RING domain 1 (BARD1) complex recognizes pre-ribosomal RNA (pre-rRNA) to coordinate the process of double-strand break (DSB) repair. However, the biological functions and molecular mechanisms under this process haven't been explained clearly. Here, we find an important pre-rRNA binding site highly conserved among BARD1 proteins. Mut…

As rates of antimicrobial resistance (AMR) among bacterial pathogens continue to rise, the discovery and development of novel classes of therapeutics that can serve as alternatives or adjuncts to traditional small-molecule antibiotics, such as monoclonal antibodies (mAbs), is a public health priority. Some of the most promising antigen targets for antibacterial mAbs are surface polysaccharides su…

The pool of free intracellular Mg²⁺ varies among tissues with the highest concentration measured in muscle tissue and the lowest measured in immune cells and in the brain. Here we investigate the impact of free Mg²⁺ on the fidelity of human DNA ligase I (LIG1). LIG1 is the major DNA ligase and is required to complete DNA replication, recombination and repair pathways. Bialle…

Obstructive sleep apnea (OSA) induces childhood cognitive impairment via chronic intermittent hypoxia (CIH), a process to which endoplasmic reticulum stress (ERS)-mediated apoptosis critically contributes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is widely recognized for its significant neuroprotective effects in various neurological diseases, yet its role in ERS-related apoptosis in pr…