Pp5

Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, protein phosphatase inhibitors have been shown to have anti-cancer activity. A prime example is the small molecule LB-100, an inhibitor of protein phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology. LB-100 has proven effective in pre-clinical models in combination with immunotherapy, but the molecular underpinnings of this synergy remain understood poorly. We report here a sensitivity of the mRNA splicing machinery to phosphorylation changes in response to LB-100 in colorectal adenocarcinoma...

BACKGROUND: Plastic waste is a global environmental issue that impacts the well-being of humans, animals, plants, and microorganisms. Microplastic contamination has been previously reported at Kung Wiman Beach, located in Chanthaburi province along with the Eastern Gulf of Thailand. Our research aimed to study the microbial population of the sand and plastisphere and isolate microorganisms with potential plastic degradation activity. METHODS: Plastic and sand samples were collected from Kung Wiman Beach for microbial isolation on agar plates...

Ovalbumin (OVA) is the principal protein constituent of eggs. As an alternative to eggs, cell-cultured OVA can reduce the environmental impact of global warming and land use. Escherichia coli Nissle 1917 (EcN), a probiotic with specific endogenous cryptic plasmids that stably exist in cells without the addition of antibiotics, was chosen as the host for the efficient heterologous expression of the OVA. OVA yield reached 20 mg·L-1 in shake flasks using the OVA expression cassette containing a tac promoter (Ptac ) upstream of the OVA-coding sequences on the endogenous plasmid pMUT2...

OBJECTIVE: To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD). METHODS: Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis...

The review describes correlations between impaired functioning of chaperones and co-chaperones in Alzheimer's disease (AD) pathogenesis. The study aims to highlight significant lines of research in this field. Chaperones like Hsp90 or Hsp70 are critical agents in regulating cell homeostasis. Due to some conditions, like aging, their activity is damaged, resulting in β-amyloid and tau aggregation. This leads to the development of neurocognitive impairment. Dysregulation of co-chaperones is one of the causes of this condition...

SUMMARY: With the increasing rates of exome and whole genome sequencing, the ability to classify large sets of germline sequencing variants using up-to-date American College of Medical Genetics-Association for Molecular Pathology (ACMG-AMP) criteria is crucial. Here, we present Automated Germline Variant Pathogenicity (AutoGVP), a tool that integrates germline variant pathogenicity annotations from ClinVar and sequence variant classifications from a modified version of InterVar (PVS1 strength adjustments, removal of PP5/BP6)...

SUMMARY: With the increasing rates of exome and whole genome sequencing, the ability to classify large sets of germline sequencing variants using up-to-date American College of Medical Genetics - Association for Molecular Pathology (ACMG-AMP) criteria is crucial. Here, we present Automated Germline Variant Pathogenicity (AutoGVP), a tool that integrates germline variant pathogenicity annotations from ClinVar and sequence variant classifications from a modified version of InterVar (PVS1 strength adjustments, removal of PP5/BP6)...

Autosomal dominant intellectual development disorder-6 (MRD6) arises from a grin2b gene mutation, inducing neurodevelopmental issues. The effects of MRD6 encompass cognitive disabilities, seizures, muscle tone decline, and autism-like traits. Its severity ranges from mild impairment to severe epilepsy. The disorder's rarity is emphasized by roughly 100 reported GRIN2B-related cases, spotlighting the gene's significance in brain development. We present the case of a three-year-old Moroccan boy who was referred to a neuropediatric department for a molecular diagnosis...

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, that promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes non-homologous end joining...

AIMS: Regular exercise training benefits cardiovascular health and effectively reduces the risk for cardiovascular disease. Circular RNAs (circRNAs) play important roles in cardiac pathophysiology. However, the role of circRNAs in response to exercise training and biological mechanisms responsible for exercise-induced cardiac protection remain largely unknown. METHODS AND RESULTS: RNA sequencing was used to profile circRNA expression in adult mouse cardiomyocytes which were isolated from mice with or without exercise training...

Serine/threonine protein phosphatases play a significant role in the survival and propagation of multiple cancers. In this issue of Cell Chemical Biology, Ahanin et al.1 demonstrate that protein phosphatase 5 (PP5) dephosphorylates and inactivates the cell death effector protein FADD independently of Hsp90, and they identify a selective PP5 inhibitor as a new therapeutic strategy for renal cancer.

To alleviate the adverse consequences of conventional planting of the rice-wheat cropping system and achieve long-term sustainability, a 3-cycle experiment (2019-2022) was conducted to investigate the effects of six planting patterns (PPs) on the grain yield and environmental performance. PP1 entailed annual rotary tillage (RT) without straw returning but without fertilization for rice and wheat seasons. PP2 was the same as PP1 but involved fertilization. PP3 was the same as PP2 but included straw return. PP4 entailed rice planting the same as in PP3, but with innovative zero-tillage (ZT) seeding technology for wheat planting...

The realization of drug detection in drug-using crime sites can provide law enforcement officials with direct evidence. This research has developed and demonstrated an easy-to-use handheld sensor that can quickly detect methamphetamine (MA) in the field. The core of the handheld UV spectrophotometer device (HUVSD) is the STM32F103 series of single-chip micro-controller, which has a 32-bit microcontroller and two embedded 12-bit high-precision analog-to-digital converter (ADC) modules. Through Bluetooth-wireless transmission protocol, the spectral information can be displayed in the cell phone's app, and it is possible to visually determine whether the test sample contains methamphetamine hydrochloride substances based on the characteristic peak at 410 nm...

The main challenges in second near-infrared region molecular fluorophores are poor water solubility and unknown long-term toxicity at present. Herein, new NIR-II molecular fluorophores have been designed and employed to integrate biocompatible pillar[5]arene with 10 outer triethylene oxide groups for the synthesis of rotaxane IRCR. In addition, PEGylated pillar[5]arenes have been combined for the self-assembly of two supramolecular vesicular systems, i.e., PP5-IR1 and PP5-IR2, affording aqueous solubility and lowered cellular toxicity...

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Meckel syndrome. METHODS: A pedigree with a history of three consecutive adverse pregnancies which presented at the First Affiliated Hospital of Zhengzhou University on August 31, 2017 was selected as the study subject. Clinical data of the pedigree were collected. High-throughput sequencing was carried out to screen for variants of ciliopathy-related genes in the third fetus following induced abortion, and candidate variant was verified by Sanger sequencing...

T4 polynucleotide kinase (T4 PNK) helps with DNA recombination and repair. In this work, a phosphate pillar[5]arene@palladium nanoparticles@reduced graphene oxide nanocomposite (PP5@PdNPs@rGO)-based electrochemical biosensor was created to identify T4 PNK activities. The PP5 used to complex toluidine blue (TB) guest molecules is water-soluble. With T4 PNK and ATP, the substrate DNA, which included a 5'-hydroxyl group, initially self-assembled over the gold electrode surface by chemical adsorption of the thiol units...

Introduction: Postoperative comprehensive treatment has become increasingly important in recent years. This study was to repair tissue defects resulting from the removal of diseased tissue and to eliminate or inhibit the recurrence and metastasis of residual tumors under the condition of reducing the systemic side effects of chemotherapeutic drugs. To address these challenges, multifunctional scaffolds based local drug delivery systems will be a promising solution. Methods: An optimal drug-loaded scaffold material PHBV-mPEG5k (PP5) was prepared, which is biocompatible, hydrophilic and biodegradable...

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Serine/threonine protein phosphatase-5 (PP5) is involved in tumor progression and survival, making it an attractive therapeutic target. Specific inhibition of protein phosphatases has remained challenging because of their conserved catalytic sites. PP5 contains its regulatory domains within a single polypeptide chain, making it a more desirable target. Here we used an in silico approach to screen and develop a selective inhibitor of PP5. Compound P053 is a competitive inhibitor of PP5 that binds to its catalytic domain and causes apoptosis in renal cancer...

Functional changes in chaperone systems play a major role in the decline of cognition and contribute to neurological pathologies, such as Alzheimer's disease (AD). While such a decline may occur naturally with age or with stress or trauma, the mechanisms involved have remained elusive. The current models suggest that amyloid-β (Aβ) plaque formation leads to the hyperphosphorylation of tau by a Hsp90-dependent process that triggers tau neurofibrillary tangle formation and neurotoxicity. Several co-chaperones of Hsp90 can influence the phosphorylation of tau, including FKBP51, FKBP52 and PP5...