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 Xiao1,2, Yutong Sun3 and Li Ma1,2

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 Caruana1,§, Luca Simula1,2,§, Franco Locatelli1,# and Silvia Campello2,3, #

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 Hengst1,2, Heiner Wedemeyer2,3,4 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 Möröy1,2,3

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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p53 and energy balance: meeting hypothalamic AgRP neurons

Omar Al-Massadi1,2,#, Mar Quiñones1,2,#, Ruben Nogueiras1,2

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 Hwang2,3 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

p38β MAPK mediates ULK1-dependent induction of autophagy in skeletal muscle of tumor-bearing mice

Zhelong Liu1, 2,†, Ka Wai Thomas Sin1,†, Hui Ding1,3, HoangAnh Amy Doan1, Song Gao1, Hongyu Miao4, Yahui Wei1,#, Yiman Wang1,#, Guohua Zhang1, and Yi-Ping Li1

INTRODUCTION Cancer has been increasingly recognized as a systemic disorder that stresses multiple organs independent of its location. At least 50% of cancer patients experience cachexia, a systemic wasting syndrome

Mitochondrial stress management: a dynamic journey

Miriam Valera-Alberni1,2 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.

Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets

Konstantin Stoletov1, Lian Willetts1, Perrin H. Beatty1 and John D. Lewis1

INTRODUCTION Currently, many cancer patients undergo chemotherapy, which is aimed at mitigating the risk of future metastasis. These treatments, however, have numerous system-wide off-target effects that negatively impact the patients’

Therapeutic anti-tumor immunity directed against neo-epitopes by intratumor delivery of mRNA encoding MLKL

Lien Van Hoecke1,2 and Xavier Saelens1,2,3

We have developed a potentially generic treatment method to induce tumor antigen-specific cellular immunity based on the transient intra-tumor expression of the necroptosis-inducing factor MLKL (Figure 1). Importantly, we have

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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

Striatal dual cholinergic /GABAergic transmission in Parkinson disease: friends or foes?

Natalia Lozovaya1, Yehezkel Ben-Ari1 and Constance Hammond1

Although constituting less than 1% of neuronal population of the striatum, cholinergic interneurons play a major role in the control of sensory integration in preparation for movements. These giant neurons

The NLRC4 inflammasome requires IRF8-dependent production of NAIPs

Ein Lee1,2, Rajendra Karki1 and Thirumala-Devi Kanneganti1

Inflammasomes orchestrate cellular responses to pathogen- or danger-associated molecular patterns by controlling the activation of caspase-1. Inflammasome activation results in enzymatically active caspase-1, which mediates the maturation and release of

Targeting LRH-1/NR5A2 to treat type 1 diabetes mellitus

Nadia Cobo-Vuilleumier1, Petra I. Lorenzo1 and Benoit R. Gauthier1

The liver receptor homolog-1 (LRH-1) is a member of the NR5A family of nuclear receptors that plays a pivotal role in early embryonic development while later on it specifies the

Nucleolar Stress: hallmarks, sensing mechanism and diseases

Kai Yang1,2, Jie Yang1 and Jing Yi1

The nucleolus is a prominent subnuclear compartment, where ribosome biosynthesis takes place. Recently, the nucleolus has gained attention for its novel role in the regulation of cellular stress. Nucleolar stress is emerging as a new concept, which is characterized by diverse cellular insult-induced abnormalities in nucleolar structure and function, ultimately leading to activation of p53 or other stress signaling pathways and alterations in cell behavior. Despite a number of comprehensive reviews on this concept, straightforward and clear-cut way criteria for a nucleolar stress state, regarding the factors that elicit this state, the morphological and functional alterations as well as the rationale for p53 activation are still missing. Based on literature of the past two decades, we herein summarize the evolution of the concept and provide hallmarks of nucleolar stress. Along with updated information and thorough discussion of existing confusions in the field, we pay particular attention to the current understanding of the sensing mechanisms (...)

Calling RNF168 to action

Somaira Nowsheen1 and Zhenkun Lou2

– [table id=103 /] – It is interesting to note that MDC1 acts as a node for the recruitment of both RNF8 and L3MBTL2 and brings these two factors into

Exosomal secretion of truncated cytosolic lysyl-tRNA synthetase induces inflammation during cell starvation

Sang Bum Kim1,2, Seongmin Cho1, 2 and Sunghoon Kim1,2

Kim et al. (2017) reveals three crucial steps of KRS secretion, including its dissociation from the MSC complex, interaction with syntenin, and secretion via the exosomal pathway (Figure 1). –

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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 Lu1,2 and Xingxu Huang1,3

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 Yamamoto1,2,3,4

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

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

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