Results 131 to 140 of about 67,820 (304)

SCF E3 Ligase Substrates Switch from CAN-D to Can-ubiquitylate

open access: yes, 2018
Liu et al. (2018) report a mathematical model predicting how the cellular repertoire of SCF E3 ligases is assembled by “adaptive exchange on demand,” with the limited pool of CUL1 scanning the vast sea of F-box proteins for those with substrates ...
Schulman, B., Scott, D.
core   +1 more source

Potent and Selective IGF‐IIR‐Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins

open access: yesAdvanced Science, EarlyView.
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

Mitochondrial stress in advanced fibrosis and cirrhosis associated with chronic hepatitis B, chronic hepatitis C, or nonalcoholic steatohepatitis

open access: yesHepatology, EarlyView., 2022
Adaptive mitochondrial mechanisms allow mitochondrial resilience and prevent the worsening of fibrosis, while deregulation of these mechanisms promotes the progression from no/minimal‐mild (F0‐F2) fibrosis to advanced fibrosis and cirrhosis (F3‐F4). Abstract Background and Aims Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters ...
Dimitri Loureiro   +17 more
wiley   +1 more source

Elevated TRIM25 Impairs Poly (ADP‐ribose) Metabolism via PARG Degradation and Mediates Compression‐Induced Intervertebral Disc Degeneration

open access: yesAdvanced Science, EarlyView.
TRIM25 acts as a multifunctional hub driving intervertebral disc degeneration under mechanical stress. Mechanical compression significantly upregulates TRIM25 expression, establishing it as a key E3 ubiquitin ligase platform. TRIM25 targets PARG and Ku80 via distinct molecular interfaces, triggering their ubiquitination and degradation.
Zhangrong Cheng   +9 more
wiley   +1 more source

Xanthatin Targets CISD1 to Drive Ferroptosis and Mitophagy as a Dual Anticancer Strategy in Triple‐Negative Breast Cancer

open access: yesAdvanced Science, EarlyView.
Triple‐negative breast cancer has a poor prognosis. Xanthatin directly targets and degrades CISD1, triggering ferroptosis through iron dysregulation. The concurrently activated mitophagy synergistically amplifies ferroptotic cell death. Xanthatin also demonstrates potent in vivo anti‐tumor efficacy with minimal toxicity, highlighting its therapeutic ...
Qinwen Liu   +9 more
wiley   +1 more source

MVP Inhibits Influenza A Virus‐Induced Ferroptosis by Targeting IRF1 and Increasing FSP1 Activity

open access: yesAdvanced Science, EarlyView.
During IAV infection, MVP inhibits IRF1 polyubiquitination, thereby relieving IRF1‐mediated transcriptional inhibition of FSP1. Consequently, this leads to an upregulation of FSP1 expression, thereby reinforcing the inhibition of ferroptosis. In addition, the MVP can promote myristoylation and ubiquitination of FSP1, enabling its membrane localization ...
Yingbo Chen   +12 more
wiley   +1 more source

Coacervate‐Mediated Lysosome‐Targeting Antibody Delivery for Protein Degradation

open access: yesAdvanced Science, EarlyView.
Targeting coacervates to the lysosome in the cytoplasm is a challenge. Here, we convert a tetrapeptide into lysosome‐targeting, membrane‐translocating coacervates. The lysosome‐sorting peptide coacervates facilitate coacervate‐mediated delivery of antibody antigen complexes and a PROTAC compound to the lysosome for the targeted degradation of cancer ...
Dingdong Yuan   +7 more
wiley   +1 more source

ERAD Component MoHrd3 Facilitates Pathogenicity and Establishes a Direct Regulation on Autophagy in Magnaporthe Oryzae

open access: yesAdvanced Science, EarlyView.
MoHrd3 plays a crucial role in regulating the pathogenicity of Magnaporthe oryzae. As an ER‐associated degradation component, MoHrd3 involves in ER stress‐triggered autophagy. It facilitates the fusion between the autophagosome and the vacuole via enhancing the interaction between MoAtg8 and MoYpt7.
Huiqing Xia   +11 more
wiley   +1 more source

Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G‐Quadruplex Resolution to Maintain DNA Repair and Tumor Survival

open access: yesAdvanced Science, EarlyView.
Glutamine deprivation triggers transient DNA damage yet activates adaptive repair in hepatocellular carcinoma cells. We identify TRIB3 as a stress‐induced nuclear scaffold that associates with DDX5 and G‐quadruplex DNA atBRCA1 andRAD51AP1 promoters. TRIB3 loss increases G4 accumulation, suppresses HR gene transcription, elevates γ‐H2A.X, and sensitizes
Qiang Ji   +10 more
wiley   +1 more source

Targeted Degradation of eEF2K by a Structure‐Guided PROTAC Strategy for the Treatment of Triple‐Negative Breast Cancer

open access: yesAdvanced Science, EarlyView.
This study developed an eEF2K‐targeting PROTAC, A6, that efficiently degrades eEF2K in TNBC cells, inhibiting tumor growth in vitro and in vivo. To enhance tumor‐specific delivery, we engineered A6@ZIF‐8, a pH‐sensitive nanocarrier, which improved drug accumulation at tumor sites, offering a promising therapeutic strategy for TNBC through targeted ...
Shijun Cao   +10 more
wiley   +1 more source

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