Results 101 to 110 of about 164,092 (257)

Inhibition of SIRT7 Overcomes Radioresistance in Pancreatic Neuroendocrine Tumors by Reactivating MEN1 Expression

open access: yesAdvanced Science, EarlyView.
Pancreatic neuroendocrine tumors frequently silence MEN1 through epigenetic mechanisms. Here, SIRT7 recruits DNMT1 to the MEN1 promoter, drives hypermethylation, and enhances DNA repair. Inhibiting SIRT7 restores MEN1, reduces MRN complex abundance, impairs double‐strand break repair, and sensitizes PanNET models to radiation, supporting SIRT7 as a ...
Jianyun Jiang   +11 more
wiley   +1 more source

Analysis of polyubiquitin conjugates reveals that the Rpn10 substrate receptor contributes to the turnover of multiple proteasome targets [PDF]

open access: yes, 2005
The polyubiquitin receptor Rpn10 targets ubiquitylated Sic1 to the 26S proteasome for degradation. In contrast, turnover of at least one ubiquitin-proteasome system (UPS) substrate, CPY*, is impervious to deletion of RPN10.
Deshaies, Raymond J.   +4 more
core   +1 more source

Molecular Glue cc‐885 Inhibits VHL‐Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation

open access: yesAdvanced Science, EarlyView.
VHL‐deficient kidney cancer lacks effective treatments. This study reveals that the molecular glue degrader cc‐885 hijacks the cellular recycling system to selectively destroy the oncogenic protein ETS1, effectively killing VHL‐mutant tumors. Combining CC‐885 with the approved drug belzutifan achieves powerful synergy, offering a promising new ...
Taowei Yang   +15 more
wiley   +1 more source

Proteasome-associated HECT-type ubiquitin ligase activity is required for plant immunity.

open access: yesPLoS Pathogens, 2018
Regulated degradation of proteins by the 26S proteasome plays important roles in maintenance and signalling in eukaryotic cells. Proteins are marked for degradation by the action of E3 ligases that site-specifically modify their substrates by adding ...
James J Furniss   +6 more
doaj   +1 more source

PSMA8‐Containing 20S Proteasome Regulates Spermiogenesis and Male Fertility

open access: yesAdvanced Science, EarlyView.
PSMA8 assembles s20S proteasome that degrades specific substrates in elongating spermatids. Degradation of s20S‐substrates activates translation of FXR1‐target mRNAs, which are essential for mitochondrial sheath formation and sperm morphogenesis.
Huiwen Cao   +7 more
wiley   +1 more source

Integration of Spatiotemporal Multi‐Omics in Peach Fruit Unravels a Metabolic Niche and the Genetic Basis of Trichome‐Mediated Stress Adaptation

open access: yesAdvanced Science, EarlyView.
This study constructed the first spatiotemporal multi‐omics map of peach fruit and discovered a key candidate gene that synergistically regulates trichome development and drought tolerance through the jasmonic acid signaling pathway, providing insights into the coupling mechanism between development and stress resistance.
Zhixin Liu   +9 more
wiley   +1 more source

TP53 R249S mutation in hepatic organoids captures the predisposing cancer risk

open access: yesHepatology, EarlyView., 2022
The systematic approach in elucidating the gain‐of‐function (GOF) roles of TP53 mutations in early liver carcinogenesis. Unique downstream targets of TP53 L3 mutations were identified from chormatin immunoprecipitation sequencing in HCC cell lines, followed by a series of validation assays to substantiate the exclusive transcriptional regulations ...
Yin Kau Lam   +10 more
wiley   +1 more source

NUDT21 Drives T‐Cell Acute Lymphoblastic Leukemia Through Dual Regulation of Alternative Polyadenylation and Transcriptional Activation

open access: yesAdvanced Science, EarlyView.
In summary, our study defines a coordinated oncogenic model in which NUDT21 integrates alternative polyadenylation–dependent UBE2D3 stabilization and transcriptional activation to sustain MYC‐driven T‐ALL cell survival, thereby establishing NUDT21 as a central regulatory node and a promising therapeutic target.
Conglian Qiu   +18 more
wiley   +1 more source

Restoring Iron Homeostasis via Smoothened Inhibition: A Novel Strategy Against Hearing Loss

open access: yesAdvanced Science, EarlyView.
 . ABSTRACT Sensorineural hearing loss (SNHL) induced by noise or aminoglycoside antibiotics is a significant public health concern without any FDA‐approved pharmaceutical therapies. Dysregulation of iron homeostasis and its subsequently induced ferroptosis has increasingly been identified as a key mechanism underlying cochlear hair cell (HC) damage ...
Huanyu Mao   +9 more
wiley   +1 more source

Proteasome dysfunction in aged human α-synuclein transgenic mice

open access: yesNeurobiology of Disease, 2006
A deficit in proteasome function in Parkinson's disease has been speculated. We characterized the ubiquitin–proteasome system in three regions of brain from transgenic and nontransgenic littermates.
Li Chen   +3 more
doaj   +1 more source

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