Results 41 to 50 of about 119,140 (262)

Novel Inhibitors for MDM2-MDM4 E3 Ligase Potently Induce p53-Indepedent Apoptosis in Drug-Resistant Leukemic Cells

open access: yesMolecules
MDM2 and MDM4 are major negative regulators of tumor suppressor p53. Beyond regulating p53, MDM2 possesses p53-independent activity in promoting cell cycle progression and tumorigenesis via its RING domain ubiquitin E3 ligase activity. MDM2 and MDM4 form
Rati Lama   +7 more
doaj   +1 more source

Stealing the spotlight: CUL4-DDB1 ubiquitin ligase docks WD40-repeat proteins to destroy

open access: yesCell Division, 2007
Recent investigation of Cullin 4 (CUL4) has ushered this class of multiprotein ubiquitin E3 ligases to center stage as critical regulators of diverse processes including cell cycle regulation, developmental patterning, DNA replication, DNA damage and ...
Zhang Hui, Higa Leigh
doaj   +1 more source

Microbiome−host proteostasis crosstalk—An emerging perspective on mechanisms and interventions toward healthy longevity

open access: yesFEBS Letters, EarlyView.
Proteostasis and the gut microbiota play a key role in shaping host physiology. Microbiota‐derived metabolites, vitamins, and RNA modulate host proteostasis. Findings from model systems, including C. elegans, indicate microbes can either stabilize or disrupt host proteostasis.
Abhishek Anil Dubey, Maria Ermolaeva
wiley   +1 more source

Pharmacophore-based ML model to filter candidate E3 ligands and predict E3 Ligase binding probabilities

open access: yesInformatics in Medicine Unlocked
Among the plethora of E3 Ligases, only a few have been utilized for the novel PROTAC technology. However, extensive knowledge of the preparation of E3 ligands and their utilization for PROTACs is already present in several databases.
Reagon Karki   +4 more
doaj   +1 more source

Rational Design and Synthesis of HSF1-PROTACs for Anticancer Drug Development

open access: yesMolecules, 2022
PROTACs employ the proteosome-mediated proteolysis via E3 ligase and recruit the natural protein degradation machinery to selectively degrade the cancerous proteins. Herein, we have designed and synthesized heterobifunctional small molecules that consist
Chiranjeev Sharma   +3 more
doaj   +1 more source

Phosphoinositides and inositol phosphates as molecular glues

open access: yesFEBS Letters, EarlyView.
Inositol phosphates (IPs) and phosphoinositides (PIPs) regulate diverse eukaryotic processes. Beyond recruiting signaling proteins or acting as structural cofactors, recent studies suggest they mediate protein–protein interactions as natural molecular glues.
Aleshia Seaton‐Terry   +9 more
wiley   +1 more source

CUL4-DDB1-CRBN E3 Ubiquitin Ligase Regulates Proteostasis of ClC-2 Chloride Channels: Implication for Aldosteronism and Leukodystrophy

open access: yesCells, 2020
Voltage-gated ClC-2 channels are essential for chloride homeostasis. Complete knockout of mouse ClC-2 leads to testicular degeneration and neuronal myelin vacuolation. Gain-of-function and loss-of-function mutations in the ClC-2-encoding human CLCN2 gene
Ssu-Ju Fu   +7 more
doaj   +1 more source

Tumour–host interactions in Drosophila: mechanisms in the tumour micro‐ and macroenvironment

open access: yesMolecular Oncology, EarlyView.
This review examines how tumour–host crosstalk takes place at multiple levels of biological organisation, from local cell competition and immune crosstalk to organism‐wide metabolic and physiological collapse. Here, we integrate findings from Drosophila melanogaster studies that reveal conserved mechanisms through which tumours hijack host systems to ...
José Teles‐Reis, Tor Erik Rusten
wiley   +1 more source

FBXL17/spastin axis as a novel therapeutic target of hereditary spastic paraplegia

open access: yesCell & Bioscience, 2022
Background Spastin significantly influences microtubule regulation in neurons and is implicated in the pathogenesis of hereditary spastic paraplegia (HSP). However, post-translational regulation of the spastin protein remains nebulous.
Hyun Mi Kang   +10 more
doaj   +1 more source

USP29‐regulated noncanonical stabilization of the hypoxia‐inducible factor‐α in aggressive prostate cancer

open access: yesMolecular Oncology, EarlyView.
We identify USP29 as the only DUB mirroring CA9 expression, a marker of hypoxia and HIF pathway activation associated with PCA aggressiveness. USP29 stabilizes HIF‐1α and HIF‐2α via a noncanonical mechanism that is independent of PHD/pVHL activity yet relies on proteasomal regulation, establishing USP29 as a previously unrecognized regulator of hypoxic
Amelie S Schober   +16 more
wiley   +1 more source

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