Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong +5 more
wiley +1 more source
Site-specific identification and quantitation of endogenous SUMO modifications under native conditions. [PDF]
Small ubiquitin-like modifier (SUMO) modification regulates numerous cellular processes. Unlike ubiquitin, detection of endogenous SUMOylated proteins is limited by the lack of naturally occurring protease sites in the C-terminal tail of SUMO proteins ...
Ahmad, Alla S +8 more
core +2 more sources
Halofuginone is a Molecular Glue Degrader of Integrin β4
Integrin β4 overexpression is linked to aggressive tumors and poor prognosis, but targeted therapies are lacking. We identified halofuginone (HF) as a molecular glue degrader that promotes integrin β4 degradation via the CRL4BWDR18 E3 ligase. HF suppresses tumor progression in vitro and in vivo, offering a new strategy for targeting oncogenic ...
Wei Gong +8 more
wiley +1 more source
Rapid degradation of mutant SLC25A46 by the ubiquitin-proteasome system results in MFN1/2-mediated hyperfusion of mitochondria. [PDF]
SCL25A46 is a mitochondrial carrier protein that surprisingly localizes to the outer membrane and is distantly related to Ugo1. Here we show that a subset of SLC25A46 interacts with mitochondrial dynamics components and the MICOS complex.
Claypool, Steven M +6 more
core +1 more source
Targeting the PDK1/c‐Myc/SOX10 Signaling in Oligodendrocytes Alleviates Neuropathic Pain
This work reveals that oligodendrocyte homeostasis, mediated by PDK1, is a critical determinant of neuropathic pain (NPP) pathogenesis. Disruption of PDK1 in oligodendrocytes impairs SOX10‐dependent myelination programs through c‐Myc accumulation, leading to disrupted myelination and the pathophysiology of NPP.
Pingping Qiao +7 more
wiley +1 more source
Role of the ubiquitin-selective CDC-48/UFD-1/NPL-4 chaperone in DNA replication [PDF]
Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. Posttranslational modifications, such as ubiquitylation, constitute a fast and effective mechanism to control such complex protein function.
Franz, André
core
ABSTRACT Gut microbiota dysbiosis promotes colorectal cancer (CRC) tumorigenesis. A global fecal metagenomic analysis identified Gemella morbillorum as a key contributor to the CRC‐associated microbiota. Fluorescence in situ hybridization revealed that Gemella morbillorum is enriched in CRC tumor tissues compared to adjacent normal tissues.
Zhen Wang +8 more
wiley +1 more source
Assessment of the direct and indirect effects of MPP+ and dopamine on the human proteasome: implications for Parkinson's disease aetiology [PDF]
Mitochondrial impairment, glutathione depletion and oxidative stress have been implicated in the pathogenesis of Parkinson’s disease (PD), linked recently to proteasomal dysfunction.
Beck, KE +5 more
core +1 more source
Lysosome‐targeting chimeras (LYTACs) enable degradation of extracellular and membrane proteins via lysosomal trafficking. We report a novel IGF‐II mutant (Del1–7, Y27L) that selectively engages IGF‐IIR while avoiding IGF‐IR and IR‐A. mutIGF‐II–based LYTACs enhance target internalization and degradation and support a genetically encodable, all‐protein ...
Yuan Zhao +16 more
wiley +1 more source
Parkin uses the UPS to ship off dysfunctional mitochondria [PDF]
Parkin is a ubiquitin E3 ligase that is implicated in familial Parkinson disease (PD). Previous studies have established its role in mitophagy, a pathway whereby dysfunctional mitochondria are targeted for autophagic degradation.
Chan, David C., Chan, Nickie C.
core

