Next-generation proteasome inhibitor oprozomib synergizes with modulators of the unfolded protein response to suppress hepatocellular carcinoma [PDF]
Hepatocellular carcinoma (HCC) responds poorly to conventional systemic therapies. The first-in-class proteasome inhibitor bortezomib has been approved in clinical use for hematologic malignancies and has shown modest activity in solid tumors, including ...
Bogaerts, Eliene +12 more
core +2 more sources
Aging Is a Key Driver for Adult Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a classical age‐related hematologic malignancy, and a key driver of AML is aging, which profoundly regulates intrinsic factors such as genomic instability, epigenetic reprogramming, and metabolic dysregulation, and alters bone marrow microenvironment.
Rong Yin, Haojian Zhang
wiley +1 more source
TP53 R249S mutation in hepatic organoids captures the predisposing cancer risk
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
The Pharmacology and Dual Role of Proteostasis in Amyloidoses
Cellular protein quality control comprises the ubiquitin proteasome system, autophagy, and molecular chaperones, which maintain proteostasis in healthy tissues.
Angela Albanese +2 more
doaj +1 more source
Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease [PDF]
The proteasome is the central component of the main cellular protein degradation pathway. During the past four decades, the critical function of the proteasome in numerous physiological processes has been revealed, and proteasome activity has been linked
Li, Jing, Sherman, David J.
core
Proteostasis by STUB1/HSP70 complex controls sensitivity to androgen receptor targeted therapy in advanced prostate cancer. [PDF]
Protein homeostasis (proteostasis) is a potential mechanism that contributes to cancer cell survival and drug resistance. Constitutively active androgen receptor (AR) variants confer anti-androgen resistance in advanced prostate cancer. However, the role
Armstrong, Cameron M +12 more
core +2 more sources
A Systematic Comparison of Alpha‐Synuclein Seed Amplification Assays for Increasing Reproducibility
ABSTRACT Seed amplification assays (SAAs) enable ultrasensitive detection of misfolded α‐synuclein across biofluids and tissues. Yet, heterogeneity in protocols limits cross‐study comparability and clinical translation. Here, we review α‐synuclein SAA methods and their performance across various biological matrices.
Manuela Amaral‐do‐Nascimento +3 more
wiley +1 more source
Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease [PDF]
Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown.
Aguzzi, Adriano +8 more
core +3 more sources
ABSTRACT Objective Variants in SLC6A1, encoding the GABA transporter 1 (GAT‐1), cause epilepsy, autism spectrum disorder, and developmental delay via loss of GABA uptake, impaired trafficking, and ER retention. We previously found that 4‐Phenylbutyrate (PBA), an FDA‐approved drug, restores GABA uptake and reduces seizures in SLC6A1‐related disorders ...
Melissa B. DeLeeuw +5 more
wiley +1 more source
Host proteostasis modulates influenza evolution [PDF]
Predicting and constraining RNA virus evolution require understanding the molecular factors that define the mutational landscape accessible to these pathogens.
Butty, Vincent L G +9 more
core +2 more sources

