Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells

Volume 2 (2018)

Cover: This month in Cell Stress: Kinase signaling in the innate immune system. Fluorescence microscopic depiction of immune cell responses within the CNS upon chronic pain. Images by Centre for Nanoscale BioPhotonics (CNBP) licensed under the CC BY 2.0 license. Image modified by Cell Stress. The cover is published under the CC BY 4.0 license.

SKP2 and OTUD1 govern non-proteolytic ubiquitination of YAP that promotes YAP nuclear localization and activity

Fan Yao¹, Zhenna Xiao^1,2, Yutong Sun³ and Li Ma^1,2

YAP and its paralog TAZ are key effectors of the evolutionarily conserved Hippo signaling pathway, a pathway that regulates organ size, tissue homeostasis, and tumorigenesis. In human cells, MST1/2 (mammalian

T lymphocytes against solid malignancies: winning ways to defeat tumours

Ignazio Caruana^1,§, Luca Simula^1,2,§, Franco Locatelli^1,# and Silvia Campello^{2,3, #}

INTRODUCTION When a tumour mass starts growing in the body, T lymphocytes are activated inside secondary lymphoid organs (SLOs) and mount an immune response against immuno-stimulating tumour antigens presented by

Irreversible impact of chronic hepatitis C virus infection on human natural killer cell diversity

Benedikt Strunz¹, Julia Hengst^1,2, Heiner Wedemeyer^2,3,4 and Niklas K. Björkström¹

Due to the fact that infection with HCV nearly always becomes chronic, we first investigated the imprint of the persisting infection on the NK cell compartment. To overcome shortcomings of

GFI1’s role in DNA repair suggests implications for tumour cell response to treatment

Charles Vadnais¹ and Tarik Möröy^1,2,3

GFI1 was discovered over 20 years ago and a large body of experimental evidence defines its function as a DNA binding transcriptional repressor. Since GFI1 does not possess any enzymatic

Mitochondrial dysfunction and its role in tissue-specific cellular stress

David Pacheu-Grau¹, Robert Rucktäschel¹ and Markus Deckers¹

Mitochondrial bioenergetics require the coordination of two different and independent genomes. Mutations in either genome will affect mitochondrial functionality and produce different sources of cellular stress. Depending on the kind of defect and stress, different tissues and organs will be affected, leading to diverse pathological conditions. There is no curative therapy for mitochondrial diseases, nevertheless, there are strategies described that fight the various stress forms caused by the malfunctioning organelles. Here, we will revise the main kinds of stress generated by mutations in mitochondrial genes and outline several ways of fighting this stress.

Alzheimer’s disease: amyloid-based pathogenesis and potential therapies

Yixiu Zhou¹, Yuhui Sun², Quan-Hong Ma² and Yaobo Liu²

INTRODUCTION Alzheimer’s disease (AD) is one of the most prevalent forms of dementia; in 2015, for example, AD affected ~46.8 million people worldwide. It is estimated that this number will

Foie gras and liver regeneration: a fat dilemma

Maria Agnese Della Fazia¹ and Giuseppe Servillo¹

The liver has a unique ability of regenerating after injuries or partial loss of its mass. The mechanisms responsible for liver regeneration – mostly occurring when the hepatic tissue is damaged or functionally compromised by metabolic stress – have been studied in considerable detail over the last few decades, because this phenomenon has both basic-biology and clinical relevance. More specifically, recent interest has been focusing on the widespread occurrence of abnormal nutritional habits in the Western world that result in an increased prevalence of non-alcoholic fatty liver disease (NAFLD). NAFLD is closely associated with insulin resistance and dyslipidemia, and it represents a major clinical challenge. The disease may progress to steatohepatitis with persistent inflammation and progressive liver damage, both of which will compromise regeneration under conditions of partial hepatectomy in surgical oncology or in liver transplantation procedures. Here, we analyze the impact of ER stress and SIRT1 in lipid metabolism and in fatty liver pathology (...)

Amelioration of obesity-induced diabetes by a novel autophagy enhancer

Hyejin Lim¹ and Myung-Shik Lee¹

Our screening system was a convenient high throughput assay of autophagic flux rather than cumulative autophagy levels, and the index of autophagic activity was calculated as the ratio of the

Epigenetic mechanisms behind cellular sensitivity to DNA damage

Amanda K. Williamson¹, Zijing Zhu¹ and Zhi-Min Yuan¹

INTRODUCTION Epigenetics is the regulation of gene expression independent of the gene sequence itself via the interactions between DNA and proteins called histones [cite]10.4161/epi.24042[/cite]. In the nucleus, DNA is highly

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The emerging role of minor intron splicing in neurological disorders

Daniel Jutzi ^1,2,+, Maureen V. Akinyi ^3,+, Jonas Mechtersheimer^1,2,+, Mikko J. Frilander³ and Marc-David Ruepp^1,4

INTRODUCTION Pre-mRNA splicing is an essential step in eukaryotic gene expression. It is predominantly a co-transcriptional process during which the non-coding introns are excised from precursor mRNA (pre-mRNA) molecules and

A new way to regulate inflammation: selective autophagic degradation of IKKγ mediated by ANGPTL8

Yu Zhang¹, Ling Zheng² and Kun Huang¹

Activation of transcription factor nuclear factor-κB (NF-κB) is one of the central events in inflammation and immunity. In resting cells, the activity of NF-κB is inhibited by its binding partner,

Rejuvenation of the aged neuromuscular junction by exercise

Tabita Kreko-Pierce^1,2 and Benjamin A. Eaton^1,2

Age-dependent declines in muscle function are observed across species. The loss of mobility resulting from the decline in muscle function represents an important health issue and a key determinant of quality of life for the elderly. It is believed that changes in the structure and function of the neuromuscular junction are important contributors to the observed declines in motor function with increased age. Numerous studies indicate that the aging muscle is an important contributor to the deterioration of the neuromuscular junction but the cellular and molecular mechanisms driving the degeneration of the synapse remain incompletely described. Importantly, growing data from both animal models and humans indicate that exercise can rejuvenate the neuromuscular junction and improve motor function. In this review we will focus on the role of muscle-derived neurotrophin signaling in the rejuvenation of the aged neuromuscular junction in response to exercise.

Salmonella Typhimurium infection: Type I Interferons integrate cellular networks to disintegrate macrophages

Nirmal Robinson^1,2

Salmonella enterica serovar Typhimurium (S. Typhimurium) are facultative intracellular bacteria that effectively evade innate immune defense mechanisms using a plethora of pathogenic principles encoded in their pathogenicity islands namely Salmonella

Centriolar satellites prevent uncontrolled degradation of centrosome proteins: a speculative review

Nicolas Lecland¹ and Andreas Merdes¹

INTRODUCTION Centrosomes are cytoplasmic structures that serve as primary microtubule organizing centers in a large variety of animal cells. They consist of a pair of cylindrically shaped centrioles, surrounded by

miR34a: a master regulator in the pathogenesis of bronchopulmonary dysplasia

Pragnya Das¹, Mansoor Ali Syed^1,2, Dilip Shah¹, Vineet Bhandari^1,3,*

BPD has been getting more attention as neonatologists from across the world are getting better in saving the lives of premature neonates. This has mobilized intense research to fill the

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Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells

Lyssia Belarif¹, Bernard Vanhove¹ and Nicolas Poirier¹

Targeting proinflammatory cytokines such as TNFα, IL-1, IL-6, is clinically beneficial in several immune-mediated inflammatory diseases (IMID). However, these cytokines are downstream mediators of immune responses that show poor impact

TRIM16 employs NRF2, ubiquitin system and aggrephagy for safe disposal of stress-induced misfolded proteins

Kautilya Kumar Jena^1,2, Subhash Mehto¹, Srinivasa Prasad Kolapalli¹, Parej Nath¹, Swati Chauhan¹ and Santosh Chauhan¹

We found that under oxidative or proteotoxic stress conditions, the TRIM16 is required for biogenesis of protein aggregates from misfolded proteins. In our attempt to investigate the mechanism by which

The role of metabolic adaptation to nutrient stress in pancreatic cancer

Abhishek Derle^1,#, Maria Chiara De Santis^1,#, Luca Gozzelino^1,#, Edoardo Ratto^1,# and Miriam Martini¹

INTRODUCTION Pancreatic cancer is the fourth leading cause of cancer death in the developed world [1]. The most common subtype of pancreatic cancer is pancreatic ductal adenocarcinomas (PDACs) that arise

Systemic signalling and local effectors in developmental stability, body symmetry, and size

Sergio Juarez-Carreño¹, Javier Morante¹ and Maria Dominguez¹

Symmetric growth and the origins of fluctuating asymmetry are unresolved phenomena of biology. Small, and sometimes noticeable, deviations from perfect bilateral symmetry reflect the vulnerability of development to perturbations. The degree of asymmetry is related to the magnitude of the perturbations and the ability of an individual to cope with them. As the left and right sides of an individual were presumed to be genetically identical, deviations of symmetry were traditionally attributed to non-genetic effects such as environmental and developmental noise. In this review, we draw attention to other possible sources of variability, especially to somatic mutations and transposons. Mutations are a major source of phenotypic variability and recent genomic data have highlighted somatic mutations as ubiquitous, even in phenotypically normal individuals. We discuss the importance of factors that are responsible for buffering and stabilizing the genome (...)

Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase

Harald Steiner^1,2, Akio Fukumori³, Shinji Tagami⁴ and Masayasu Okochi⁴

Alzheimer´s disease (AD) is a devastating neurodegenerative disease of the elderly population. Genetic evidence strongly suggests that aberrant generation and/or clearance of the neurotoxic amyloid-β peptide (Aβ) is triggering the disease. Aβ is generated from the amyloid precursor protein (APP) by the sequential cleavages of β- and γ-secretase. The latter cleavage by γ-secretase, a unique and fascinating four-component protease complex, occurs in the APP transmembrane domain thereby releasing Aβ species of 37-43 amino acids in length including the longer, highly pathogenic peptides Aβ42 and Aβ43. The lack of a precise understanding of Aβ generation as well as of the functions of other γ-secretase substrates has been one factor underlying the disappointing failure of γ-secretase inhibitors in clinical trials, but on the other side also been a major driving force for structural and in depth mechanistic studies on this key AD drug target in the past few years. Here we (...)

Mechanisms and therapeutic significance of autophagy modulation by antipsychotic drugs

Ljubica Vucicevic¹, Maja Misirkic-Marjanovic¹, Ljubica Harhaji-Trajkovic¹, Nadja Maric² and Vladimir Trajkovic³

INTRODUCTION The term autophagy (‘self-eating’ in Greek) refers to a group of evolutionarily conserved homeostatic mechanisms employed by eukaryotic cells to eliminate aged, unused, and damaged cytoplasmic components through lysosomal

p53 and energy balance: meeting hypothalamic AgRP neurons

Omar Al-Massadi^1,2,#, Mar Quiñones^1,2,#, Ruben Nogueiras^1,2

Cancer cells undergo profound metabolic changes to cope with the high energy demand for cell growth and division. Given the importance of this metabolic reprogramming in tumor development, it seems

Attenuating MKRN1 E3 ligase-mediated AMPKα suppression increases tolerance against metabolic stresses in mice

Hyunji Han¹, Sehyun Chae², Daehee Hwang^2,3 and Jaewhan Song¹

The signaling pathways instigated by the activation of AMP-activated protein kinase (AMPK) play major roles in balancing the energy levels in cells as well as in the whole-body system by

Mitochondrial stress management: a dynamic journey

Miriam Valera-Alberni^1,2 and Carles Canto¹

Mitochondria undergo continuous challenges in the course of their life, from their generation to their degradation. These challenges include the management of reactive oxygen species, the proper assembly of mitochondrial respiratory complexes and the need to balance potential mutations in the mitochondrial DNA. The detection of damage and the ability to keep it under control is critical to fine-tune mitochondrial function to the organismal energy needs. In this review, we will analyze the multiple mechanisms that safeguard mitochondrial function in light of in crescendo damage. This sequence of events will include initial defense against excessive reactive oxygen species production, compensation mechanisms by the unfolded protein response (UPRmt), mitochondrial dynamics and elimination by mitophagy.

Astrocytes, emerging stars of energy homeostasis

Simonetta Camandola¹

INTRODUCTION The brain is the organ responsible for the centralized control of the other organs’ functions and, in higher vertebrates, of reasoning. Such tasks are achieved thanks to the interconnections

Base editors: a powerful tool for generating animal models of human diseases

Zongyang Lu^1,2 and Xingxu Huang^1,3

BASE EDITORS: A NOVEL GENOME ENGINEERING TOOL Genetically engineered mouse models of human diseases have long been used in understanding the underlying mechanisms of the clinically relevant genetic disorders. In

Unweaving the role of nuclear Lamins in neural circuit integrity

Samantha L. Deal¹ and Shinya Yamamoto^1,2,3,4

Structural integrity of the nuclear membrane is essential for the homeostasis of eukaryotic cells. Critical components of this process are Lamins or type-V intermediate filament proteins that form a meshwork

Alzheimer’s disease: amyloid-based pathogenesis and potential therapies

Yixiu Zhou¹, Yuhui Sun², Quan-Hong Ma² and Yaobo Liu²

INTRODUCTION Alzheimer’s disease (AD) is one of the most prevalent forms of dementia; in 2015, for example, AD affected ~46.8 million people worldwide. It is estimated that this number will

Membrane closure in stress induced-autophagosome formation

Eiji Morita¹

Autophagy (macroautophagy) is a bulk degradation system that sequesters cytoplasmic components by generating double-layered isolation membranes and delivering these isolated contents to the lysosomes [cite]10.1146/annurev-cellbio-092910-154005[/cite]. Though this pathway was originally

Centriolar satellites prevent uncontrolled degradation of centrosome proteins: a speculative review

Nicolas Lecland¹ and Andreas Merdes¹

Novel role of the SIRT4-OPA1 axis in mitochondrial quality control

Alexander Lang¹ and Roland P. Piekorz¹

Aging is defined by various molecular and cellular hallmarks, among them stem cell exhaustion, genomic instability, altered proteostasis, cellular senescence, and mitochondrial dysfunction [cite]10.1016/j.cell.2013.05.039[/cite]. Mitochondrial defects are considered major drivers