scholarly journals Mechanisms of Cotranslational Protein Maturation in Bacteria

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiří Koubek ◽  
Jaro Schmitt ◽  
Carla Veronica Galmozzi ◽  
Günter Kramer
Keyword(s):  
Protein Synthesis ◽  
Current Knowledge ◽  
Protein Complexes ◽  
General Strategy ◽  
Protein Maturation ◽  
Processing Enzymes ◽  
Chaperone Network ◽  
Cellular Compartments ◽  
Dynamic Interplay

Growing cells invest a significant part of their biosynthetic capacity into the production of proteins. To become functional, newly-synthesized proteins must be N-terminally processed, folded and often translocated to other cellular compartments. A general strategy is to integrate these protein maturation processes with translation, by cotranslationally engaging processing enzymes, chaperones and targeting factors with the nascent polypeptide. Precise coordination of all factors involved is critical for the efficiency and accuracy of protein synthesis and cellular homeostasis. This review provides an overview of the current knowledge on cotranslational protein maturation, with a focus on the production of cytosolic proteins in bacteria. We describe the role of the ribosome and the chaperone network in protein folding and how the dynamic interplay of all cotranslationally acting factors guides the sequence of cotranslational events. Finally, we discuss recent data demonstrating the coupling of protein synthesis with the assembly of protein complexes and end with a brief discussion of outstanding questions and emerging concepts in the field of cotranslational protein maturation.

scholarly journals Biological functions controlled by manganese redox changes in mononuclear Mn-dependent enzymes

2017 ◽  
Vol 61 (2) ◽  
pp. 259-270 ◽  
Author(s):  
Wen Zhu ◽  
Nigel G.J. Richards
Keyword(s):  
Catalytic Mechanism ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Redox Properties ◽  
Metal Ligands ◽  
Manganese Ion ◽  
Hydrogen Bonding Interactions ◽  
Catalytically Active ◽  
Protein Environment

Remarkably few enzymes are known to employ a mononuclear manganese ion that undergoes changes in redox state during catalysis. Many questions remain to be answered about the role of substrate binding and/or protein environment in modulating the redox properties of enzyme-bound Mn(II), the nature of the dioxygen species involved in the catalytic mechanism, and how these enzymes acquire Mn(II) given that many other metal ions in the cell form more stable protein complexes. Here, we summarize current knowledge concerning the structure and mechanism of five mononuclear manganese-dependent enzymes: superoxide dismutase, oxalate oxidase (OxOx), oxalate decarboxylase (OxDC), homoprotocatechuate 3,4-dioxygenase, and lipoxygenase (LOX). Spectroscopic measurements and/or computational studies suggest that Mn(III)/Mn(II) are the catalytically active oxidation states of the metal, and the importance of ‘second-shell’ hydrogen bonding interactions with metal ligands has been demonstrated for a number of examples. The ability of these enzymes to modulate the redox properties of the Mn(III)/Mn(II) couple, thereby allowing them to generate substrate-based radicals, appears essential for accessing diverse chemistries of fundamental importance to organisms in all branches of life.

scholarly journals Inflammasome Activation in Pulmonary Arterial Hypertension

2022 ◽  
Vol 8 ◽  
Author(s):  
Anna Foley ◽  
Benjamin E. Steinberg ◽  
Neil M. Goldenberg
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Inflammasome Activation ◽  
Downstream Effectors ◽  
Inflammatory Stimuli ◽  
Affected Tissue ◽  
Pulmonary Arterial

Inflammasomes are multi-protein complexes that sense both infectious and sterile inflammatory stimuli, launching a cascade of responses to propagate danger signaling throughout an affected tissue. Recent studies have implicated inflammasome activation in a variety of pulmonary diseases, including pulmonary arterial hypertension (PAH). Indeed, the end-products of inflammasome activation, including interleukin (IL)-1β, IL-18, and lytic cell death (“pyroptosis”) are all key biomarkers of PAH, and are potentially therapeutic targets for human disease. This review summarizes current knowledge of inflammasome activation in immune and vascular cells of the lung, with a focus on the role of these pathways in the pathogenesis of PAH. Special emphasis is placed on areas of potential drug development focused on inhibition of inflammasomes and their downstream effectors.

scholarly journals Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion

2020 ◽  
Vol 21 (18) ◽  
pp. 6841
Author(s):  
Mafalda Escobar-Henriques ◽  
Vincent Anton
Keyword(s):  
Membrane Fusion ◽  
Cell Cycle Regulation ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Cellular Viability ◽  
Mitochondrial Quality Control ◽  
Cellular Processes ◽  
Mitochondrial Regulation ◽  
Cycle Regulation

Cdc48/p97 is a ring-shaped, ATP-driven hexameric motor, essential for cellular viability. It specifically unfolds and extracts ubiquitylated proteins from membranes or protein complexes, mostly targeting them for proteolytic degradation by the proteasome. Cdc48/p97 is involved in a multitude of cellular processes, reaching from cell cycle regulation to signal transduction, also participating in growth or death decisions. The role of Cdc48/p97 in endoplasmic reticulum-associated degradation (ERAD), where it extracts proteins targeted for degradation from the ER membrane, has been extensively described. Here, we present the roles of Cdc48/p97 in mitochondrial regulation. We discuss mitochondrial quality control surveillance by Cdc48/p97 in mitochondrial-associated degradation (MAD), highlighting the potential pathologic significance thereof. Furthermore, we present the current knowledge of how Cdc48/p97 regulates mitofusin activity in outer membrane fusion and how this may impact on neurodegeneration.

scholarly journals Molecular Regulation of Cell Fate in Cerebral Ischemia: Role of the Inflammasome and Connected Pathways

2014 ◽  
Vol 34 (12) ◽  
pp. 1857-1867 ◽  
Author(s):  
George Trendelenburg
Keyword(s):  
Cell Fate ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Sterile Inflammation ◽  
Inflammasome Activation ◽  
Stroke Incidence ◽  
Multifactorial Diseases ◽  
Relevant Role ◽  
Metabolic Conditions

Analogous to Toll-like receptors, NOD-like receptors represent a class of pattern recognition receptors, which are cytosolic and constitute part of different inflammasomes. These large protein complexes are activated not only by different pathogens, but also by sterile inflammation or by specific metabolic conditions. Mutations can cause hereditary autoinflammatory systemic diseases, and inflammasome activation has been linked to many multifactorial diseases, such as diabetes or cardiovascular diseases. Increasing data also support an important role in different central nervous diseases such as stroke. Thus, the current knowledge of the functional role of this intracellular ‘master switch’ of inflammation is discussed with a focus on its role in ischemic stroke, neurodegeneration, and also with regard to the recent data which argues for a relevant role in other organs or biologic systems which influence stroke incidence or prognosis.

scholarly journals The Functional Role of Long Non-Coding RNAs in Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4848
Author(s):  
Michal Wozniak ◽  
Malgorzata Czyz
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Close Association ◽  
Response To Treatment ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Molecular Events ◽  
Melanoma Treatment

Melanoma is the most lethal skin cancer, with increasing incidence worldwide. The molecular events that drive melanoma development and progression have been extensively studied, resulting in significant improvements in diagnostics and therapeutic approaches. However, a high drug resistance to targeted therapies and adverse effects of immunotherapies are still a major challenge in melanoma treatment. Therefore, the elucidation of molecular mechanisms of melanomagenesis and cancer response to treatment is of great importance. Recently, many studies have revealed the close association of long noncoding RNAs (lncRNAs) with the development of many cancers, including melanoma. These RNA molecules are able to regulate a plethora of crucial cellular processes including proliferation, differentiation, migration, invasion and apoptosis through diverse mechanisms, and even slight dysregulation of their expression may lead to tumorigenesis. lncRNAs are able to bind to protein complexes, DNA and RNAs, affecting their stability, activity, and localization. They can also regulate gene expression in the nucleus. Several functions of lncRNAs are context-dependent. This review summarizes current knowledge regarding the involvement of lncRNAs in melanoma. Their possible role as prognostic markers of melanoma response to treatment and in resistance to therapy is also discussed

scholarly journals RNA-Binding Proteins and the Complex Pathophysiology of ALS

2021 ◽  
Vol 22 (5) ◽  
pp. 2598
Author(s):  
Wanil Kim ◽  
Do-Yeon Kim ◽  
Kyung-Ha Lee
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Dynamic Function ◽  
Disease Related Genes ◽  
Cellular Dysfunction ◽  
Lateral Sclerosis

Genetic analyses of patients with amyotrophic lateral sclerosis (ALS) have identified disease-causing mutations and accelerated the unveiling of complex molecular pathogenic mechanisms, which may be important for understanding the disease and developing therapeutic strategies. Many disease-related genes encode RNA-binding proteins, and most of the disease-causing RNA or proteins encoded by these genes form aggregates and disrupt cellular function related to RNA metabolism. Disease-related RNA or proteins interact or sequester other RNA-binding proteins. Eventually, many disease-causing mutations lead to the dysregulation of nucleocytoplasmic shuttling, the dysfunction of stress granules, and the altered dynamic function of the nucleolus as well as other membrane-less organelles. As RNA-binding proteins are usually components of several RNA-binding protein complexes that have other roles, the dysregulation of RNA-binding proteins tends to cause diverse forms of cellular dysfunction. Therefore, understanding the role of RNA-binding proteins will help elucidate the complex pathophysiology of ALS. Here, we summarize the current knowledge regarding the function of disease-associated RNA-binding proteins and their role in the dysfunction of membrane-less organelles.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Prospective Memory Development Across the Lifespan

2020 ◽  
Vol 25 (3) ◽  
pp. 162-173 ◽  
Author(s):  
Sascha Zuber ◽  
Matthias Kliegel
Keyword(s):  
Prospective Memory ◽  
Healthy Aging ◽  
Present Model ◽  
Current Knowledge ◽  
Well Being ◽  
The Elderly ◽  
Cognitive Factors ◽  
Everyday Functioning ◽  
Integrative Framework

Abstract. Prospective Memory (PM; i.e., the ability to remember to perform planned tasks) represents a key proxy of healthy aging, as it relates to older adults’ everyday functioning, autonomy, and personal well-being. The current review illustrates how PM performance develops across the lifespan and how multiple cognitive and non-cognitive factors influence this trajectory. Further, a new, integrative framework is presented, detailing how those processes interplay in retrieving and executing delayed intentions. Specifically, while most previous models have focused on memory processes, the present model focuses on the role of executive functioning in PM and its development across the lifespan. Finally, a practical outlook is presented, suggesting how the current knowledge can be applied in geriatrics and geropsychology to promote healthy aging by maintaining prospective abilities in the elderly.

Resveratrol: A new potential therapeutic agent for melanoma?

2019 ◽  
Vol 26 ◽  
Author(s):  
Mohamad Hossein Pourhanifeh ◽  
Kazem Abbaszadeh-Goudarzi ◽  
Mohammad Goodarzi ◽  
Sara G.M. Piccirillo ◽  
Alimohammad Shafiee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Therapeutic Agent ◽  
Current Knowledge ◽  
Treatment Resistance ◽  
Anti Cancer ◽  
Apoptosis Inducer ◽  
Life Threatening ◽  
First Time

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

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