scholarly journals SWI/SNF Complex Mutations in Gynecologic Cancers: Molecular Mechanisms and Models

2020 ◽  
Vol 15 (1) ◽  
pp. 467-492 ◽  
Author(s):  
Yemin Wang ◽  
Lien Hoang ◽  
Jennifer X. Ji ◽  
David G. Huntsman
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Wide Spectrum ◽  
Gynecologic Cancer ◽  
Tumor Development ◽  
Gynecologic Cancers ◽  
Genes Encoding ◽  
Genomic Studies ◽  
Histologic Types

The SWI/SNF (mating type SWItch/Sucrose NonFermentable) chromatin remodeling complexes interact with histones and transcription factors to modulate chromatin structure and control gene expression. These evolutionarily conserved multisubunit protein complexes are involved in regulating many biological functions, such as differentiation and cell proliferation. Genomic studies have revealed frequent mutations of genes encoding multiple subunits of the SWI/SNF complexes in a wide spectrum of cancer types, including gynecologic cancers. These SWI/SNF mutations occur at different stages of tumor development and are restricted to unique histologic types of gynecologic cancers. Thus, SWI/SNF mutations have to function in the appropriate tissue and cell context to promote gynecologic cancer initiation and progression. In this review, we summarize the current knowledge of SWI/SNF mutations in the development of gynecologic cancers to provide insights into both molecular pathogenesis and possible treatment implications for these diseases.

scholarly journals Regulatory factors for the assembly of thylakoid membrane protein complexes

2012 ◽  
Vol 367 (1608) ◽  
pp. 3420-3429 ◽  
Author(s):  
Wei Chi ◽  
Jinfang Ma ◽  
Lixin Zhang
Keyword(s):  
Membrane Protein ◽  
Thylakoid Membrane ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Thylakoid Membranes ◽  
Regulatory Factors ◽  
Photosynthetic Organisms ◽  
Photosynthetic Complexes ◽  
Membrane Protein Complexes

Major multi-protein photosynthetic complexes, located in thylakoid membranes, are responsible for the capture of light and its conversion into chemical energy in oxygenic photosynthetic organisms. Although the structures and functions of these photosynthetic complexes have been explored, the molecular mechanisms underlying their assembly remain elusive. In this review, we summarize current knowledge of the regulatory components involved in the assembly of thylakoid membrane protein complexes in photosynthetic organisms. Many of the known regulatory factors are conserved between prokaryotes and eukaryotes, whereas others appear to be newly evolved or to have expanded predominantly in eukaryotes. Their specific features and fundamental differences in cyanobacteria, green algae and land plants are discussed.

scholarly journals RNA Polymerase III Subunit Mutations in Genetic Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Elisabeth Lata ◽  
Karine Choquet ◽  
Francis Sagliocco ◽  
Bernard Brais ◽  
Geneviève Bernard ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Rna Polymerase Iii ◽  
Initiation Factor ◽  
Varicella Zoster ◽  
Vital Functions ◽  
Genes Encoding ◽  
Pol Iii

RNA polymerase (Pol) III transcribes small untranslated RNAs such as 5S ribosomal RNA, transfer RNAs, and U6 small nuclear RNA. Because of the functions of these RNAs, Pol III transcription is best known for its essential contribution to RNA maturation and translation. Surprisingly, it was discovered in the last decade that various inherited mutations in genes encoding nine distinct subunits of Pol III cause tissue-specific diseases rather than a general failure of all vital functions. Mutations in the POLR3A, POLR3C, POLR3E and POLR3F subunits are associated with susceptibility to varicella zoster virus-induced encephalitis and pneumonitis. In addition, an ever-increasing number of distinct mutations in the POLR3A, POLR3B, POLR1C and POLR3K subunits cause a spectrum of neurodegenerative diseases, which includes most notably hypomyelinating leukodystrophy. Furthermore, other rare diseases are also associated with mutations in genes encoding subunits of Pol III (POLR3H, POLR3GL) and the BRF1 component of the TFIIIB transcription initiation factor. Although the causal relationship between these mutations and disease development is widely accepted, the exact molecular mechanisms underlying disease pathogenesis remain enigmatic. Here, we review the current knowledge on the functional impact of specific mutations, possible Pol III-related disease-causing mechanisms, and animal models that may help to better understand the links between Pol III mutations and disease.

scholarly journals Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 235 ◽  
Author(s):  
Miguel Rodrigo ◽  
Hana Buchtelova ◽  
Ana Jimenez ◽  
Pavlina Adam ◽  
Petr Babula ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuroblastoma Cell Line ◽  
Scoring Functions ◽  
Bafilomycin A1 ◽  
Development Of Resistance ◽  
Genes Encoding ◽  
Response To Stress

The efficiency of cisplatin (CDDP) is significantly hindered by the development of resistance during the treatment course. To gain a detailed understanding of the molecular mechanisms underlying the development of cisplatin resistance, we comparatively analyzed established a CDDP-resistant neuroblastoma cell line (UKF-NB-4CDDP) and its susceptible parental cells (UKF-NB-4). We verified increased chemoresistance of UKF-NB-4CDDP cells by analyzing the viability, induction of apoptosis and clonal efficiency. To shed more light on this phenomenon, we employed custom cDNA microarray (containing 2234 probes) to perform parallel transcriptomic profiling of RNA and identified that 139 genes were significantly up-regulated due to CDDP chemoresistance. The analyses of molecular pathways indicated that the top up-regulation scoring functions were response to stress, abiotic stimulus, regulation of metabolic process, apoptotic processes, regulation of cell proliferation, DNA repair or regulation of catalytic activity, which was also evidenced by analysis of molecular functions revealing up-regulation of genes encoding several proteins with a wide-spectrum of enzymatic activities. Functional analysis using lysosomotropic agents chloroquine and bafilomycin A1 validated their potential to re-sensitize UKF-NB-4CDDP cells to CDDP. Taken together, the identification of alterations in specific genes and pathways that contribute to CDDP chemoresistance may potentially lead to a renewed interest in the development of novel rational therapeutics and prognostic biomarkers for the management of CDDP-resistant neuroblastoma.

scholarly journals Transcriptome analysis reveals rice MADS13 as an important repressor of the carpel development pathway in ovules

2020 ◽  
Author(s):  
Michela Osnato ◽  
Elia Lacchini ◽  
Alessandro Pilatone ◽  
Ludovico Dreni ◽  
Andrea Grioni ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Protein Complexes ◽  
Female Sterility ◽  
Homeotic Genes ◽  
Ovule Development ◽  
Knock Out ◽  
Regulatory Pathways ◽  
Genes Encoding

Abstract In angiosperms, floral homeotic genes encoding MADS-domain transcription factors regulate the development of floral organs. Specifically, members of the SEPALLATA (SEP) and AGAMOUS (AG) subfamilies form higher-order protein complexes to control floral meristem determinacy and to specify the identity of female reproductive organs. In rice, the AG subfamily gene OsMADS13 is intimately involved in the determination of ovule identity, since knock-out mutant plants develop carpel-like structures in place of ovules, resulting in female sterility. Little is known about the regulatory pathways at the base of rice gynoecium development. To investigate molecular mechanisms acting downstream of OsMADS13, we obtained transcriptomes of immature inflorescences from wild-type and Osmads13 mutant plants. Among a total of 476 differentially expressed genes (DEGs), a substantial overlap with DEGs from the SEP-family Osmads1 mutant was found, suggesting that OsMADS1 and OsMADS13 may act on a common set of target genes. Expression studies and preliminary analyses of two up-regulated genes encoding Zinc-finger transcription factors indicated that our dataset represents a valuable resource for the identification of both OsMADS13 target genes and novel players in rice ovule development. Taken together, our study suggests that OsMADS13 is an important repressor of the carpel pathway during ovule development.

Inflammasomes in the Pathophysiology of Maternal Obesity: Potential Therapeutic Targets to Reduce Long-Term Adverse Health Outcomes in the Mother and Offspring

2020 ◽  
Vol 19 (2) ◽  
pp. 165-175
Author(s):  
Padma Murthi ◽  
Gayathri Rajaraman
Keyword(s):  
Health Outcomes ◽  
Molecular Mechanisms ◽  
Maternal Obesity ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Reproductive Age ◽  
Adverse Health ◽  
Adverse Health Outcomes ◽  
Self Assembling ◽  
Prevalence Of Obesity

: Over the past 20 years, the prevalence of obesity has risen dramatically worldwide, with an increase in occurrence among women in their reproductive age. Obesity during pregnancy is associated with significantly increased maternal and fetal morbidity and mortality. In addition to the short-term adverse health outcomes, both mother and the child are prone to develop cardiovascular, metabolic and neurological disorders. Although associations between obesity during pregnancy and adverse maternalfetal health outcomes are clear, the complex molecular mechanisms underlying maternal obesity remain largely unknown. This review describes multimeric self-assembling protein complexes, namely inflammasomes, as potential molecular targets in the pathophysiology of maternal obesity. Inflammasomes are implicated in both normal physiological and in pathophysiological processes that occur in response to an inflammatory milieu throughout gestation. This review highlights the current knowledge of inflammasome expression and its activity in pregnancies affected by maternal obesity. Key discussions in defining pharmacological inhibition of upstream as well as downstream targets of the inflammasome signaling cascade; and the inflammasome platform, as a potential therapeutic strategy in attenuating the pathophysiology underpinning inflammatory component in maternal obesity are presented herein.

scholarly journals Biochemical and Molecular Aspects of Phosphorus Limitation in Diatoms and Their Relationship with Biomolecule Accumulation

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 565
Author(s):  
José Pablo Lovio-Fragoso ◽  
Damaristelma de Jesús-Campos ◽  
José Antonio López-Elías ◽  
Luis Ángel Medina-Juárez ◽  
Diana Fimbres-Olivarría ◽  
...  
Keyword(s):  
Extracellular Polymeric Substances ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Calvin Cycle ◽  
Phosphorus Limitation ◽  
P Deficiency ◽  
Carbon Structures ◽  
Genes Encoding ◽  
Molecular Aspects ◽  
Molecular And Biochemical Mechanisms

Diatoms are the most abundant group of phytoplankton, and their success lies in their significant adaptation ability to stress conditions, such as nutrient limitation. Phosphorus (P) is a key nutrient involved in the transfer of energy and the synthesis of several cellular components. Molecular and biochemical mechanisms related to how diatoms cope with P deficiency are not clear, and research into this has been limited to a few species. Among the molecular responses that have been reported in diatoms cultured under P deficient conditions is the upregulation of genes encoding enzymes related to the transport, assimilation, remobilization and recycling of this nutrient. Regarding biochemical responses, due to the reduction of the requirements for carbon structures for the synthesis of proteins and phospholipids, more CO2 is fixed than is consumed by the Calvin cycle. To deal with this excess, diatoms redirect the carbon flow toward the synthesis of storage compounds such as triacylglycerides and carbohydrates, which are excreted as extracellular polymeric substances. This review aimed to gather all current knowledge regarding the biochemical and molecular mechanisms of diatoms related to managing P deficiency in order to provide a wider insight into and understanding of their responses, as well as the metabolic pathways affected by the limitation of this nutrient.

scholarly journals Molecular Mechanism of Global Genome Nucleotide Excision Repair

Acta Naturae ◽  
2014 ◽  
Vol 6 (1) ◽  
pp. 23-34 ◽  
Author(s):  
I. O. Petruseva ◽  
A. N. Evdokimov ◽  
O. I. Lavrik
Keyword(s):  
Nucleotide Excision Repair ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Excision Repair ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Double Helix ◽  
Repair Synthesis ◽  
Nucleotide Excision ◽  
Dna Repair Synthesis

Nucleotide excision repair (NER) is a multistep process that recognizes and eliminates a wide spectrum of damage causing significant distortions in the DNA structure, such as UV-induced damage and bulky chemical adducts. The consequences of defective NER are apparent in the clinical symptoms of individuals affected by three disorders associated with reduced NER capacities: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). These disorders have in common increased sensitivity to UV irradiation, greatly elevated cancer incidence (XP), and multi-system immunological and neurological disorders. The eucaryotic NER system eliminates DNA damage by the excision of 24-32 nt single-strand oligonucleotides from a damaged strand, followed by restoration of an intact double helix by DNA repair synthesis and DNA ligation. About 30 core polypeptides are involved in the entire repair process. NER consists of two pathways distinct in initial damage sensor proteins: transcription-coupled repair (TC-NER) and global genome repair (GG-NER). The article reviews current knowledge on the molecular mechanisms underlying damage recognition and its elimination from mammalian DNA.

scholarly journals Recent insights into the molecular mechanisms of the NLRP3 inflammasome activation

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1469 ◽  
Author(s):  
Tomasz Próchnicki ◽  
Matthew S. Mangan ◽  
Eicke Latz
Keyword(s):  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Current Model ◽  
Adaptor Protein ◽  
Death Process ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Molecular Events

Inflammasomes are high-molecular-weight protein complexes that are formed in the cytosolic compartment in response to danger- or pathogen-associated molecular patterns. These complexes enable activation of an inflammatory protease caspase-1, leading to a cell death process called pyroptosis and to proteolytic cleavage and release of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Along with caspase-1, inflammasome components include an adaptor protein, ASC, and a sensor protein, which triggers the inflammasome assembly in response to a danger signal. The inflammasome sensor proteins are pattern recognition receptors belonging either to the NOD-like receptor (NLR) or to the AIM2-like receptor family. While the molecular agonists that induce inflammasome formation by AIM2 and by several other NLRs have been identified, it is not well understood how the NLR family member NLRP3 is activated. Given that NLRP3 activation is relevant to a range of human pathological conditions, significant attempts are being made to elucidate the molecular mechanism of this process. In this review, we summarize the current knowledge on the molecular events that lead to activation of the NLRP3 inflammasome in response to a range of K+ efflux-inducing danger signals. We also comment on the reported involvement of cytosolic Ca2+ fluxes on NLRP3 activation. We outline the recent advances in research on the physiological and pharmacological mechanisms of regulation of NLRP3 responses, and we point to several open questions regarding the current model of NLRP3 activation.

scholarly journals An update on the diversity, ecology and biogeography of the Saccharomyces genus

2020 ◽  
Vol 20 (3) ◽  
Author(s):  
Haya Alsammar ◽  
Daniela Delneri
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Phenotypic Diversity ◽  
Evolutionary Process ◽  
Cellular Biology ◽  
Natural Environments ◽  
Wild Strains ◽  
Genomic Studies ◽  
History Of ◽  
Species Hybrids

ABSTRACT Saccharomyces cerevisiae is the most extensively studied yeast and, over the last century, provided insights on the physiology, genetics, cellular biology and molecular mechanisms of eukaryotes. More recently, the increase in the discovery of wild strains, species and hybrids of the genus Saccharomyces has shifted the attention towards studies on genome evolution, ecology and biogeography, with the yeast becoming a model system for population genomic studies. The genus currently comprises eight species, some of clear industrial importance, while others are confined to natural environments, such as wild forests devoid from human domestication activities. To date, numerous studies showed that some Saccharomyces species form genetically diverged populations that are structured by geography, ecology or domestication activity and that the yeast species can also hybridize readily both in natural and domesticated environments. Much emphasis is now placed on the evolutionary process that drives phenotypic diversity between species, hybrids and populations to allow adaptation to different niches. Here, we provide an update of the biodiversity, ecology and population structure of the Saccharomyces species, and recapitulate the current knowledge on the natural history of Saccharomyces genus.

scholarly journals Roles and Mechanisms of Deubiquitinases (DUBs) in Breast Cancer Progression and Targeted Drug Discovery

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 965
Author(s):  
Sixuan Li ◽  
Hongquan Zhang ◽  
Xiaofan Wei
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Prognostic Indicators ◽  
Breast Cancer Patients ◽  
Oncogenic Signaling

Deubiquitinase (DUB) is an essential component in the ubiquitin—proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. Here, we review current knowledge about the effects and molecular mechanisms of DUBs in breast cancer, providing novel insight into treatments of breast cancer-targeting DUBs.

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