Commander Complex—A Multifaceted Operator in Intracellular Signaling and Cargo

Commander complex is a 16-protein complex that plays multiple roles in various intracellular events in endosomal cargo and in the regulation of cell homeostasis, cell cycle and immune response. It consists of COMMD1–10, CCDC22, CCDC93, DENND10, VPS26C, VPS29, and VPS35L. These proteins are expressed ubiquitously in the human body, and they have been linked to diseases including Wilson’s disease, atherosclerosis, and several types of cancer. In this review we describe the function of the commander complex in endosomal cargo and summarize the individual known roles of COMMD proteins in cell signaling and cancer. It becomes evident that commander complex might be a much more important player in intracellular regulation than we currently understand, and more systematic research on the role of commander complex is required.

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Multiple roles of PIWIL1 in mouse neocorticogenesis

10.1101/106070 ◽

2017 ◽

Cited By ~ 6

Author(s):

Barbara Viljetic ◽

Liyang Diao ◽

Jixia Liu ◽

Zeljka Krsnik ◽

Sagara H.R. Wijeratne ◽

...

Keyword(s):

Cell Cycle ◽

Small Rna ◽

Radial Glia ◽

Multiple Roles ◽

Small Rna Sequencing ◽

Knock Out ◽

Deep Layers ◽

Pirna Pathway ◽

The Brain

AbstractPIWI-interacting RNAs (piRNAs) and their associated PIWI proteins play an important role in repressing transposable elements in animal germlines. However, little is known about the function of PIWI proteins and piRNAs in the developing brain. Here, we investigated the role of an important PIWI family member, Piwi-like protein 1 (Piwil1; also known as Miwi in mouse) in the developing mouse neocortex. Using a Piwil1 knock-out (Piwil1 KO) mouse strain, we found that Piwil1 is essential for several steps of neocorticogenesis, including neocortical cell cycle, neuron migration and dendritogenesis. Piwil1 deletion resulted in increased cell cycle re-entry at embryonic day 17 (E17) when predominantly intracortically projecting neurons are being produced. Prenatal Piwil1 deletion increased the number of Pax6+ radial glia at postnatal day 0 (P0). Furthermore, Piwil1 deletion disrupted migration of Satb2+ neurons within deep layers at E17, P0 and P7. Satb2+ neurons showed increased co-localization with Bcl11b (also known as Ctip2), marker of subcortically projecting neurons. Piwil1 knockouts had disrupted neocortical circuitry represented by thinning of the corpus callosum and altered dendritogenesis. We further investigated if Piwil1 deletion disrupted expression levels of neocortical piRNAs by small RNA-sequencing in neocortex. We did not find differential expression of piRNAs in the neocortices of Piwil1 KO, while differences were observed in other Piwil1 KO tissues. This result suggests that Piwil1 may act independently of piRNAs and have novel roles in higher cognitive centers, such as neocortex. In addition, we report a screen of piRNAs derived from tRNA fragments in developing neocortices. Our result is the first report of selective subsets of piRNAs and tRNA fragments in developing prenatal neocortices and helps clarify some outstanding questions about the role of the piRNA pathway in the brain.

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Molecular Politics, Wearables, and the Aretaic Shift in Biopolitical Governance

Theory Culture & Society ◽

10.1177/0263276419894053 ◽

2020 ◽

Vol 37 (3) ◽

pp. 71-96

Author(s):

Peter Lindner

Keyword(s):

Human Body ◽

Common Ground ◽

New Technologies ◽

Expert Knowledge ◽

The Body ◽

Life Itself ◽

The Common ◽

The Individual ◽

Individual Body

Since the publication of Nikolas Rose’s ‘The Politics of Life Itself’ (2001) there has been vivid discussion about how biopolitical governance has changed over the last decades. This article uses what Rose terms ‘molecular politics’, a new socio-technical grip on the human body, as a contrasting background to ask anew his question ‘What, then, of biopolitics today?’ – albeit focusing not on advances in genetics, microbiology, and pharmaceutics, as he does, but on the rapid proliferation of wearables and other sensor-software gadgets. In both cases, new technologies providing information about the individual body are the common ground for governance and optimization, yet for the latter, the target is habits of moving, eating and drinking, sleeping, working and relaxing. The resulting profound differences are carved out along four lines: ‘somatic identities’ and a modified understanding of the body; the role of ‘expert knowledge’ compared to that of networks of peers and self-experimentation; the ‘types of intervention’ by which new technologies become effective in our everyday life; and the ‘post-discipline character’ of molecular biopolitics. It is argued that, taken together, these differences indicate a remarkable shift which could be termed aretaic: its focus is not ‘life itself’ but ‘life as it is lived’, and its modality are new everyday socio-technical entanglements and their more-than-human rationalities of (self-)governance.

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Caffeine as a Factor Influencing the Functioning of the Human Body—Friend or Foe?

Nutrients ◽

10.3390/nu13093088 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3088

Author(s):

Kamil Rodak ◽

Izabela Kokot ◽

Ewa Maria Kratz

Keyword(s):

Human Body ◽

The Elderly ◽

Negative Effects ◽

Caffeine Consumption ◽

The Central Nervous System ◽

Disease Entities ◽

The Individual ◽

Available Information ◽

The Impact

Nowadays, caffeine is one of the most commonly consumed substances, which presents in many plants and products. It has both positive and negative effects on the human body, and its activity concerns a variety of systems including the central nervous system, immune system, digestive system, respiratory system, urinary tract, etc. These effects are dependent on quantity, the type of product in which caffeine is contained, and also on the individual differences among people (sex, age, diet etc.). The main aim of this review was to collect, present, and analyze the available information including the latest discoveries on the impact of caffeine on human health and the functioning of human body systems, taking into account the role of caffeine in individual disease entities. We present both the positive and negative sides of caffeine consumption and the healing properties of this purine alkaloid in diseases such as asthma, Parkinson’s disease, and others, not forgetting about the negative effects of excess caffeine (e.g., in people with hypertension, children, adolescents, and the elderly). In summary, we can conclude, however, that caffeine has a multi-directional influence on various organs of the human body, and because of its anti-oxidative properties, it was, and still is, an interesting topic for research studies including those aimed at developing new therapeutic strategies.

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The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control

International Journal of Molecular Sciences ◽

10.3390/ijms21030709 ◽

2020 ◽

Vol 21 (3) ◽

pp. 709

Author(s):

Javier Manzano-López ◽

Fernando Monje-Casas

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Current Knowledge ◽

Cell Cycle Control ◽

Multiple Roles ◽

Special Focus ◽

Cyclin Dependent Kinase ◽

Yeast Saccharomyces Cerevisiae ◽

Cycle Progression

The Cdc14 phosphatase is a key regulator of mitosis in the budding yeast Saccharomyces cerevisiae. Cdc14 was initially described as playing an essential role in the control of cell cycle progression by promoting mitotic exit on the basis of its capacity to counteract the activity of the cyclin-dependent kinase Cdc28/Cdk1. A compiling body of evidence, however, has later demonstrated that this phosphatase plays other multiple roles in the regulation of mitosis at different cell cycle stages. Here, we summarize our current knowledge about the pivotal role of Cdc14 in cell cycle control, with a special focus in the most recently uncovered functions of the phosphatase.

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Using the Biology of Chronic Lymphocytic Leukemia to Choose Treatment

Hematology ◽

10.1182/asheducation-2011.1.104 ◽

2011 ◽

Vol 2011 (1) ◽

pp. 104-109 ◽

Cited By ~ 20

Author(s):

Peter Hillmen

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Intracellular Signaling ◽

Residual Disease ◽

Lymphocytic Leukemia ◽

High Dose ◽

Signaling Mechanisms ◽

The Individual ◽

First Time ◽

Targeted Approach

AbstractIn recent years, our understanding of the pathophysiology of chronic lymphocytic leukemia (CLL) has advanced significantly. It is now clear that CLL is a relatively proliferative disorder that requires the help of its microenvironment to be maintained and to progress. The stimulation of the CLL cell occurs in most, if not all, patients through antigen stimulation via the BCR. In addition, there is now a clearer appreciation of the role of the p53 pathway leading to chemoresistance. These insights are allowing a more targeted approach with the use of p53-independent drugs such as mAbs and high-dose steroids to overcome genetically poor-risk CLL. The elucidation of the molecular and intracellular signaling mechanisms of disease is just beginning to facilitate the development of several targeted small molecules that promise to revolutionize the treatment of CLL. The measurement of the level of minimal residual disease (MRD) in CLL is becoming more available, facilitating approaches in which the aim of therapy is the eradication of detectable MRD. This also promises to improve personalization of therapy to the individual. Recently, the addition of rituximab to fludarabine plus cyclophosphamide (FCR) has improved overall survival in CLL for the first time, and it appears that this will only be the first small step on the path to much more effective therapies and, hopefully, less toxic targeted therapies.

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SMARCB1 Acts as a Quiescent Gatekeeper for Cell Cycle and Immune Response in Human Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21113969 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3969 ◽

Cited By ~ 1

Author(s):

Sung Kyung Choi ◽

Myoung Jun Kim ◽

Jueng Soo You

Keyword(s):

Cell Cycle ◽

Immune Response ◽

Cell Lines ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Fetal Lung ◽

Human Cells ◽

Lung Fibroblasts ◽

General Role

Switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, one of the adenosine triphosphate (ATP)-dependent chromatin remodeler complexes. The unique role of SMARCB1 has been reported in various cellular contexts. Here, we focused on the general role of the ubiquitous expression of SMARCB1 in a normal cell state. We selected ARPE19 (human primary retinal pigment epithelium) and IMR90 (from human fetal lung fibroblasts) cell lines as they have completely different contexts. Furthermore, although these cell lines have been immortalized, they are relatively close to normal human cells. The loss of SMARCB1 in ARPE19 and IMR90 cells reduced cell cycle progression via the upregulation of P21. Transcriptome analysis followed by SMARCB1 knockdown in both cell lines revealed that SMARCB1 was not only involved in cell maintenance but also conferred immunomodulation. Of note, SMARCB1 bound to interleukin (IL) 6 promoter in a steady state and dissociated in an active immune response state, suggesting that SMARCB1 was a direct repressor of IL6, which was further confirmed via loss- and gain-of-function studies. Taken together, we demonstrated that SMARCB1 is a critical gatekeeper molecule of the cell cycle and immune response.

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Nutrition and immunity: lessons for COVID-19

Nutrition and Diabetes ◽

10.1038/s41387-021-00165-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Philip C. Calder

Keyword(s):

Immune Response ◽

Immune System ◽

Older People ◽

Susceptibility To Infection ◽

Multiple Factors ◽

Good Nutrition ◽

The Individual ◽

Poor Nutrition ◽

Inflammatory Component

AbstractThe role of the immune system is to protect the individual against pathogenic organisms. Nutrition is one of multiple factors that determines the immune response and good nutrition is important in supporting the immune response. Immunity can be impaired in older people, particularly those who are frail, in those living with obesity, in those who are malnourished and in those with low intakes of micronutrients. The immune impairments associated with nutritional inadequacy increase susceptibility to infection and permit infections to become more severe, even fatal. The adverse impact of poor nutrition on the immune system, including its inflammatory component, may be one of the explanations for the higher risk of more severe outcomes from infection with SARS-CoV-2 seen in older people and in those living with obesity. Studies of individual micronutrients including vitamin D and zinc suggest roles in reducing severity of infection with SARS-CoV-2. Good nutrition is also important in promoting a diverse gut microbiota, which in turn supports the immune system. The importance of nutrition in supporting the immune response also applies to assuring robust responses to vaccination. There are many lessons from the study of nutrition and immunity that are relevant for the battle with SARS-CoV-2.

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Antioxidant intervention does not affect the response of plasma erythropoietin to short-term normobaric hypoxia in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00803.2003 ◽

2004 ◽

Vol 96 (3) ◽

pp. 1231-1235 ◽

Cited By ~ 8

Author(s):

A. M. Niess ◽

E. Fehrenbach ◽

I. Lorenz ◽

A. Müller ◽

H. Northoff ◽

...

Keyword(s):

Intracellular Signaling ◽

Individual Variability ◽

Normobaric Hypoxia ◽

Short Term ◽

Maximum Increase ◽

Oxygen Fraction ◽

The Individual ◽

Male Subjects ◽

Inspired Oxygen

Recent research has demonstrated that reactive oxygen species (ROS) participate in intracellular signaling processes initiated during hypoxia. We investigated the role of ROS in the response of plasma erythropoietin (Epo) to short-term normobaric hypoxia in humans. Twelve male subjects were exposed twice to 4 h of normobaric hypoxia (H; inspired oxygen fraction 12.5%) with a period of 6 wk between both experiments (H1 and H2). With the use of a randomized placebo-controlled crossover design, the subjects received orally a combination of the antioxidants all-rac-α-tocopherol (800 mg/day for 3 wk) and α-lipoic acid (600 mg/day for 2 wk) or placebo before H1 and H2, respectively. Three weeks before H1, the subjects underwent one control experiment in normoxia (N; inspired oxygen fraction 20.9%) without any treatment. Serum α-tocopherol was significantly higher after treatment with antioxidants compared with placebo. Capillary Po2 declined during H without significant differences between antioxidants and placebo. Plasma peroxide levels were lower under antioxidant treatment but not affected by hypoxia. The response of Epo to H did not show significant differences between antioxidant [maximum increase (means, 95% confidence interval): +121%, +66 to +176%] and placebo conditions (+108%, +68 to +149%). Similarly, hypoxia-induced increase of Epo corrected for diurnal variations, as revealed during N, did not differ between antioxidants and placebo. Individual variability of Epo in response to H was not related to the individual degree of hypoxemia during H. Our results do not support the assumption that ROS play a major modulating role in the response of Epo to short-term normobaric hypoxia in humans.

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The scientific research progress of novel coronavirus—— SARS-COV-2

E3S Web of Conferences ◽

10.1051/e3sconf/202124503052 ◽

2021 ◽

Vol 245 ◽

pp. 03052

Author(s):

LiuQing Yang

Keyword(s):

Immune Response ◽

Host Cell ◽

Human Body ◽

Host Cells ◽

Research Progress ◽

Rna Molecules ◽

The World ◽

Novel Coronavirus ◽

Clear Idea

A COVID-19 outbreak suddenly appeared in Wuhan, China, in December 2019, and then spread around the world quickly. So far, there have been a series of studies on SARS-COV-2 which has been confirmed as the cause of the outbreak. On account of the characteristic of spreading in droplet, SARS-COV-2 could be transmitted from person to person, causing the epidemic to become more and more severe all over the world. For SARS-COV-2, the spike S protein is essential for successfully infecting cells. In fact, most developmental strategies of vaccines are based on the structure of S proteins as well as host cell receptors. There are also vaccines based on the role of RNA molecules of SARS-COV-2 in host cells or the immune response of human body against the virus. This paper summarizes some research results of scholars on SARS-COV-2, aiming to provide people with a clear idea to understand SARS-COV-2, and hoping to make some contributions to the fight against the virus.

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The methyltransferase SETD6 regulates Mitotic progression through PLK1 methylation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1804407116 ◽

2019 ◽

Vol 116 (4) ◽

pp. 1235-1240 ◽

Cited By ~ 13

Author(s):

Michal Feldman ◽

Zlata Vershinin ◽

Inna Goliand ◽

Natalie Elia ◽

Dan Levy

Keyword(s):

Cell Cycle ◽

Intracellular Signaling ◽

Cellular Proliferation ◽

Lysine Methylation ◽

Mitotic Progression ◽

Nonhistone Proteins ◽

Proteomic Screen ◽

Lysine Residues ◽

Cycle Regulation

Lysine methylation, catalyzed by protein lysine methyltransferases (PKMTs), is a key player in regulating intracellular signaling pathways. However, the role of PKMTs and the methylation of nonhistone proteins during the cell cycle are largely unexplored. In a recent proteomic screen, we identified that the PKMT SETD6 methylates PLK1—a key regulator of mitosis and highly expressed in tumor cells. In this study, we provide evidence that SETD6 is involved in cell cycle regulation. SETD6-deficient cells were observed to progress faster through the different mitotic steps toward the cytokinesis stage. Mechanistically, we found that during mitosis SETD6 binds and methylates PLK1 on two lysine residues: K209 and K413. Lack of methylation of these two residues results in increased kinase activity of PLK1, leading to accelerated mitosis and faster cellular proliferation, similarly to SETD6-deficient cells. Taken together, our findings reveal a role for SETD6 in regulating mitotic progression, suggesting a pathway through which SETD6 methylation activity contributes to normal mitotic pace.

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