Dubs

BACKGROUND: Ubiquitin-specific proteases (UBPs) are a large family of deubiquitinating enzymes (DUBs). They are widespread in plants and are critical for plant growth, development, and response to external stresses. However, there are few studies on the functional characteristics of the UBP gene family in the important staple crop, maize (Zea mays L.). RESULTS: In this study, we performed a bioinformatic analysis of the entire maize genome and identified 45 UBP genes...

The ubiquitin-proteasome system is essential to all eukaryotes and has been shown to be critical to parasite survival as well, including Plasmodium falciparum , the causative agent of the deadliest form of malarial disease. Despite the central role of the ubiquitin-proteasome pathway to parasite viability across its entire life-cycle, specific inhibitors targeting the individual enzymes mediating ubiquitin attachment and removal do not currently exist. The ability to disrupt P. falciparum growth at multiple developmental stages is particularly attractive as this could potentially prevent both disease pathology, caused by asexually dividing parasites, as well as transmission which is mediated by sexually differentiated parasites...

Molecular glues are typically small chemical molecules that act at the interface between a target protein and degradation machinery to trigger ternary complex formation. Identifying molecular glues is challenging. There is a scarcity of target-specific upregulating molecular glues, which are highly anticipated for numerous targets, including P53. P53 is degraded in proteasomes through polyubiquitination by specific E3 ligases, whereas deubiquitinases (DUBs) remove polyubiquitination conjugates to counteract these E3 ligases...

Förster resonance energy transfer (FRET) spectrometry is a method for determining the quaternary structure of protein oligomers from distributions of FRET efficiencies that are drawn from pixels of fluorescence images of cells expressing the proteins of interest. FRET spectrometry protocols currently rely on obtaining spectrally resolved fluorescence data from intensity-based experiments. Another imaging method, fluorescence lifetime imaging microscopy (FLIM), is a widely used alternative to compute FRET efficiencies for each pixel in an image from the reduction of the fluorescence lifetime of the donors caused by FRET...

Ubiquitin-specific protease 30 (USP30) is a deubiquitinating enzyme (DUB) localized at the mitochondrial outer membrane and involved in PINK1/Parkin-mediated mitophagy, pexophagy, BAX/BAK-dependent apoptosis, and IKKβ-USP30-ACLY-regulated lipogenesis/tumorigenesis. A USP30 inhibitor, MTX652, has recently entered clinical trials as a potential treatment for mitochondrial dysfunction. Small molecule activity-based probes (ABPs) for DUBs have recently emerged as powerful tools for in-cell inhibitor screening and DUB activity analysis, and here, we report the first small molecule ABPs (IMP-2587 and IMP-2586) which can profile USP30 activity in cells...

Per- and polyfluoroalkyl substances (PFAS) have become internationally recognized over the past three decades as persistent organic pollutants used in the production of various consumer and industrial goods. Research efforts continue to gauge the risk that historically used, and newly produced, PFAS may cause to human health. Numerous studies report toxic effects of PFAS on the human liver as well as increased serum cholesterol levels in adults. A major concern with PFAS, also dubbed "forever chemicals", is that they accumulate in liver and kidney and persist in serum...

BACKGROUND: Ubiquitination is an enzymatic modification involving ubiquitin chains, that can be reversed by deubiquitination (DUB) enzymes. Ubiquitin-specific protease 7 (USP7), which is also known as herpes virus-associated ubiquitin-specific protease (HAUSP), has been shown to play a vital role in cardiovascular diseases. However, the underlying molecular mechanism by which USP7 regulates cardiomyocyte function has not been reported. METHODS: To understand the physiological function of USP7 in the heart, we constructed cardiomyocyte-specific USP7 conditional knockout mice...

BACKGROUND: Computed tomography angiography (CTA) and digital subtraction angiography (DSA) usually raise the risk of potential malignancies with cumulative radiation doses. Current time-of-flight magnetic resonance angiography (TOF-MRA) (dubbed as cTOF), which is based on Cartesian sampling mode, may show limited diagnostic conspicuity at sinuous or branching regions. It is also prone to relatively high false positive diagnoses and undesirable display of distal intracranial vessels. This study aimed to use spiral TOF-MRA (sTOF) as a noninvasive alternative to explore possible improvement, such that the application of magnetic resonance angiography (MRA) can be extended to facilitate clinical examination or cerebrovascular disease diagnosis and follow-up studies...

A new method for the fully generalized reconstruction of three-dimensional (3D) photoproduct distributions from velocity-map imaging (VMI) projection data is presented. This approach, dubbed Fourier-Hankel-Abel Nyquist-limited TOMography (FHANTOM), builds on recent previous work in tomographic image reconstruction [C. Sparling and D. Townsend, J. Chem. Phys. 157, 114201 (2022)] and takes advantage of the fact that the distributions produced in typical VMI experiments can be simply described as a sum over a small number of spherical harmonic functions...

In vivo, muscle and neuronal cells are post-mitotic, and their function is predominantly regulated by proteostasis, a multilayer molecular process that maintains a delicate balance of protein homeostasis. The ubiquitin-proteasome system (UPS) is a key regulator of proteostasis. A dysfunctional UPS is a hallmark of muscle ageing and is often impacted in neuromuscular disorders (NMDs). Malfunction of the UPS often results in aberrant protein accumulation which can lead to protein aggregation and/or mis-localization affecting its function...

Ubiquitination and deubiquitination are important forms of posttranslational modification that govern protein homeostasis. Deubiquitinating enzymes (DUBs), a protein superfamily consisting of more than 100 members, deconjugate ubiquitin chains from client proteins to regulate cellular homeostasis. However, the dysregulation of DUBs is reportedly associated with several diseases, including cancer. The tumor microenvironment (TME) is a highly complex entity comprising diverse noncancerous cells (e.g., immune cells and stromal cells) and the extracellular matrix (ECM)...

In the age of telehealth medicine, an individual's facial features may provide the only physical clues signaling the presence of a heritable cancer predisposition syndrome. These syndromes include APC -associated polyposis, Birt-Hogg-Dubé syndrome, CYLD cutaneous syndrome, hereditary leiomyomatosis and renal cell cancer, multiple endocrine neoplasia, neurofibromatosis type 1, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome, and tuberous sclerosis complex 1 and 2, among others. Correctly identifying characteristic features is important for genetic and nongenetic specialists as early detection can enable prompt intervention, improving patient outcomes...

OTULIN encodes an eponymous linear deubiquitinase (DUB), which through the regulation of M1-Ub dynamics, is essential for controlling inflammation as a negative regulator of the canonical NF-𝛋B signaling pathway. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections...

Med1 binds to a nuclear receptor and regulates transcription. Elevated Med1 protein expression promotes cancer growth in hormone-dependent breast and prostate cancers. Med1 protein expression was investigated by deubiquitinating enzymes (DUBs) overexpression in breast cancer cell lines. Various DNA constructs of SRT-DUBs were overexpressed in the MCF7 cell line, and Med1 protein expression was investigated by western blotting. The cell growth and in vitro invasion assay were performed in BRCA1-associated protein 1 (BAP1) wild type and mutant (C91A) overexpressed cells...

The endoplasmic reticulum (ER) serves as a hub for various essential cellular processes, and maintaining ER homeostasis is essential for cell function. Reticulophagy is a selective process that removes impaired ER subdomains through autophagosome and lysosomal degradation. While the involvement of ubiquitination in autophagy regulation is well-established, its role in reticulophagy remains unclear. In this study, we screened deubiquitinating enzymes (DUBs) involved in reticulophagy and identified USP20 (ubiquitin specific peptidase 20) as a key regulator of reticulophagy under starvation conditions...

Phages play an essential role in controlling bacterial populations. Those infecting Pelagibacterales (SAR11), the dominant bacteria in surface oceans, have been studied in silico and by cultivation attempts. However, little is known about the quantity of phage-infected cells in the environment. Using fluorescence in situ hybridization techniques, we here show pelagiphage-infected SAR11 cells across multiple global ecosystems and present evidence for tight community control of pelagiphages on the SAR11 hosts in a case study...

This article studies an emerging practical problem called heterogeneous prototype learning (HPL). Unlike the conventional heterogeneous face synthesis (HFS) problem that focuses on precisely translating a face image from a source domain to another target one without removing facial variations, HPL aims at learning the variation-free prototype of an image in the target domain while preserving the identity characteristics. HPL is a compounded problem involving two cross-coupled subproblems, that is, domain transfer and prototype learning (PL), thus making most of the existing HFS methods that simply transfer the domain style of images unsuitable for HPL...

Optical fibers aim to image in vivo biological processes. In this context, high spatial resolution and stability to fiber movements are key to enable decision-making processes (e.g. for microendoscopy). Recently, a single-pixel imaging technique based on a multicore fiber photonic lantern has been designed, named computational optical imaging using a lantern (COIL). A proximal algorithm based on a sparsity prior, dubbed SARA-COIL, has been further proposed to solve the associated inverse problem, to enable image reconstructions for high resolution COIL microendoscopy...

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6...

Unknown image deformation and few-shot issues have posed significant challenges to inverse synthetic aperture radar (ISAR) target classification. To achieve robust feature representation and precise correlation modeling, this article proposes a novel two-stage few-shot ISAR classification network, dubbed as robust embedding and manifold inference (REMI). In the robust embedding stage, a multihead spatial transformation network (MH-STN) is designed to adjust unknown image deformations from multiple perspectives...