Volume 3 (2019)
The primary cilium protein folliculin is part of the autophagy signaling pathway to regulate epithelial cell size in response to fluid flow
Naïma Zemirli1,2,#, Asma Boukhalfa1,2,#, Nicolas Dupont1,2, Joëlle Botti1,3, Patrice Codogno1,2 and Etienne Morel1,2
Autophagy is a conserved molecular pathway directly involved in the degradation and recycling of intracellular components. Autophagy is associated with a response to stress situations, such as nutrients deficit, chemical toxicity, mechanical stress or microbial host defense. We have recently shown that primary cilium-dependent autophagy is important to control kidney epithelial cell size in response to fluid flow induced shear stress. Here we show that the ciliary protein folliculin (FLCN) actively participates to the signaling cascade leading to the stimulation of fluid flow-dependent autophagy upstream of the cell size regulation in HK2 kidney epithelial cells. The knockdown of FLCN induces a shortening of the primary cilium, inhibits the activation of AMPK and the recruitment of the autophagy protein ATG16L1 at the primary cilium. Altogether, our results suggest that FLCN (...)
Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response
Facundo Ramos1, María Teresa Villoria1, Esmeralda Alonso-Rodríguez1 and Andrés Clemente-Blanco1
INTRODUCTION Cells are constantly suffering endogenous and exogenous stresses that affect the integrity of the genetic material. It has been estimated that every cell of our body is exposed to
Hepatic stress associated with pathologies characterized by disturbed glucose production
Monika Gjorgjieva1-3,#, Gilles Mithieux1-3 and Fabienne Rajas1-3
LIVER FUNCTION IN GLUCOSE PRODUCTION AND NORMOGLYCEMIA Maintaining normal glucose levels in the organism i.e. between 0.7 to 1.1 g/L, is a complex task, involving a multi-organ crosstalk responsible for
Could de-stressing the brain be the solution for long-term weight loss?
Florian Seyfried1 and Mohammed K. Hankir2
INTRODUCTION One just needs to take a look at a typical vending machine (often found in hospitals) to appreciate what has happened to our food and drink. The relatively sudden
Development of novel methods that monitor necroptosis and the release of DAMPs at the single cell resolution
Hiroyasu Nakano1,2, Shin Murai1, Yoshifumi Yamaguchi3, Yoshitaka Shirasaki4,5, Osamu Nakabayashi1 and Soh Yamazaki1
HOW DOES SMART SENSE THE EXECUTION OF NECROPTOSIS? Various types of cells undergo necroptosis following stimulation with death ligands including tumor necrosis factor, Fas ligand, and TRAIL, or polyI:C, and
R-loops: formation, function, and relevance to cell stress
David F Allison1,2 and Gang Greg Wang1,2
INTRODUCTION A variety of topological, structural and hybridization events occur during DNA replication and gene transcription. Unwinding of the DNA double helix provides access for polymerase to a template strand,
P4HA1 is a new regulator of the HIF-1 pathway in breast cancer
Ren Xu1,2
Prolyl hydroxylation is a very common posttranslational protein modification. About 4% amino acid residues in animal proteins are hydroxyproline, and most of hydroxyproline is within collagen. Regulation of protein stability
Control of nucleolar stress and translational reprogramming by lncRNAs
Yvessa Verheyden1, Lucas Goedert1,2 and Eleonora Leucci1
INTRODUCTION Unfavourable environmental conditions trigger cellular responses that help minimize and/or repair the damage experienced by the cell. During stress responses, most of the biosynthetic processes of the cell are
The role of keratins in modulating carcinogenesis via communication with cells of the immune system
Inês Sequeira1 and Fiona M. Watt1
The connection between inflammation and cancer has been well established; however, little is known about the underlying mechanisms in the context of keratin loss. Keratins belong to a large family
Mitochondrial stress delays tumorigenesis in a Li-Fraumeni syndrome mouse model
Matthew P. Donnelly1, Jie Li1 and Paul M. Hwang1
As a prominent hub of metabolic activity, the mitochondrion can initiate retrograde signaling in response to bioenergetic stress that is important for various adaptive changes including cell cycle regulation [1][2].
Mitochondria organize the cellular proteostatic response and promote cellular senescence
Yanjun Li1, Lei Liu2, Yushan Zhu1 and Quan Chen1,2
Timely disposal and degradation of misfolded proteins and their aggregates is critical for cellular proteostasis and the well-being of a cell. During evolution, cells have acquired a sophisticated system to
The primary cilium protein folliculin is part of the autophagy signaling pathway to regulate epithelial cell size in response to fluid flow
Naïma Zemirli1,2,#, Asma Boukhalfa1,2,#, Nicolas Dupont1,2, Joëlle Botti1,3, Patrice Codogno1,2 and Etienne Morel1,2
Autophagy is a conserved molecular pathway directly involved in the degradation and recycling of intracellular components. Autophagy is associated with a response to stress situations, such as nutrients deficit, chemical toxicity, mechanical stress or microbial host defense. We have recently shown that primary cilium-dependent autophagy is important to control kidney epithelial cell size in response to fluid flow induced shear stress. Here we show that the ciliary protein folliculin (FLCN) actively participates to the signaling cascade leading to the stimulation of fluid flow-dependent autophagy upstream of the cell size regulation in HK2 kidney epithelial cells. The knockdown of FLCN induces a shortening of the primary cilium, inhibits the activation of AMPK and the recruitment of the autophagy protein ATG16L1 at the primary cilium. Altogether, our results suggest that FLCN (...)
Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response
Facundo Ramos1, María Teresa Villoria1, Esmeralda Alonso-Rodríguez1 and Andrés Clemente-Blanco1
INTRODUCTION Cells are constantly suffering endogenous and exogenous stresses that affect the integrity of the genetic material. It has been estimated that every cell of our body is exposed to
Hepatic stress associated with pathologies characterized by disturbed glucose production
Monika Gjorgjieva1-3,#, Gilles Mithieux1-3 and Fabienne Rajas1-3
LIVER FUNCTION IN GLUCOSE PRODUCTION AND NORMOGLYCEMIA Maintaining normal glucose levels in the organism i.e. between 0.7 to 1.1 g/L, is a complex task, involving a multi-organ crosstalk responsible for
The role of epigenetics in hypothalamic energy balance control: implications for obesity
Arnaud Obri1 and Marc Claret1,2
INTRODUCTION The prevalence of obesity continues to increase worldwide. This trend is of concern because of its dramatic economic impact, concomitant decreased lifespan and increased comorbidities, such as hypertension, cardiovascular
Remodeling of mitochondrial morphology and function: an emerging hallmark of cellular reprogramming
Anuj Rastogi1, Piyush Joshi2,3, Ela Contreras1 and Vivian Gama1,2,3,4
Research in the stem cell field has traditionally focused on understanding key transcriptional factors that provide pluripotent cell identity. However, much less is known about other critical non-transcriptional signaling networks that govern stem cell identity. Although we continue to gain critical insights into the mechanisms underlying mitochondrial morphology and function during cellular reprogramming – the process of reverting the fate of a differentiated cell into a stem cell, many uncertainties remain. Recent studies suggest an emerging landscape in which mitochondrial morphology and function have an active role in maintaining and regulating changes in cell identity. In this review, we will focus on these emerging concepts as crucial modulators of cellular reprogramming. Recognition of the widespread applicability of these concepts will increase our understanding of the mitochondrial mechanisms involved in cell identity, cell fate and disease.
The sensing of mitochondrial DAMPs by non-immune cells
Aida Rodríguez-Nuevo1,2,3 and Antonio Zorzano1,2,3
MITOCHONDRIA ARE IMMUNOGENIC ORGANELLES The efficiency of the innate immune system is determined by the capacity of distinct cell types to discriminate self from non-self structures. The dysregulation of this
Biology and clinical relevance of EpCAM
Laura Keller1,§, Stefan Werner1,§ and Klaus Pantel1
INTRODUCTION The EpCAM protein was discovered almost 40 years ago as a major epithelial carcinoma antigen by M. Herlyn and colleagues, as a result of its property to generate monoclonal
Recent progress in the role of autophagy in neurological diseases
Tian Meng1,#, Shiyin Lin1,#, Haixia Zhuang1, Haofeng Huang2, Zhengjie He1, Yongquan Hu1, Qing Gong3 and Du Feng1
Autophagy (here refers to macroautophagy) is a catabolic pathway by which large protein aggregates and damaged organelles are first sequestered into a double-membraned structure called autophagosome and then delivered to lysosome for destruction. Recently, tremendous progress has been made to elucidate the molecular mechanism and functions of this essential cellular metabolic process. In addition to being either a rubbish clearing system or a cellular surviving program in response to different stresses, autophagy plays important roles in a large number of pathophysiological conditions, such as cancer, diabetes, and especially neurodegenerative disorders. Here we review recent progress in the role of autophagy in neurological diseases and discuss how dysregulation of autophagy initiation, autophagosome formation, maturation, and/or autophagosome-lysosomal fusion step contributes to the pathogenesis of these disorders in the nervous system.
Tissue-resident memory T cells orchestrate tumour-immune equilibrium
Simone L. Park1, Laura K. Mackay1, Jason Waithman2 and Thomas Gebhardt1
EPICUTANEOUS MELANOMA INOCULATION: A MODEL OF TUMOUR-IMMUNE EQUILIBRIUM In order to study immune responses to skin cancer, B16 melanoma cells have traditionally been grafted to mice via intradermal or subcutaneous
Constitutional Mosaic Epimutations – a hidden cause of cancer?
Per E. Lønning1,2, Hans P. Eikesdal1,2, Inger M. Løes1,2 and Stian Knappskog1,2
Silencing of tumor suppressor genes by promoter hypermethylation is a key mechanism to facilitate cancer progression in many malignancies. While promoter hypermethylation can occur at later stages of the carcinogenesis process, constitutional methylation of key tumor suppressors may be an initiating event whereby cancer is started. Constitutional BRCA1 methylation due to cis-acting germline genetic variants is associated with a high risk of breast and ovarian cancer. However, this seems to be a rare event, restricted to a very limited number of families. In contrast, mosaic constitutional BRCA1 methylation is detected in 4-7% of newborn females without germline BRCA1 mutations. While the cause of such methylation is poorly understood, mosaic normal tissue BRCA1 methylation is associated with a 2-3 fold increased risk of high-grade serous ovarian cancer (HGSOC). As such, BRCA1 methylation may be the cause of a significant number of ovarian cancers. Given the molecular similarities between HGSOC and basal-like breast cancer, the (...)
LTX-315 – a promising novel antitumor peptide and immunotherapeutic agent
Dagmar Zweytick1,2
Host defense in mammals, as provided by the innate immune system, comprises proteins such as lactoferrin (LF), a multifunctional iron-binding glycoprotein originally discovered in bovine milk. LF is further pepsin-cleaved
Anti-regulatory T cells are natural regulatory effector T cells
Niels Ødum 1
It is well established that the immune system uses regulatory immune-suppressive cells to inhibit and terminate immune reactions and maintain immune balance. In the last decade, Andersen and colleagues have
The targeting of tumor-associated macrophages by vaccination
Mads Hald Andersen1,2,3
Immune suppressive myeloid cells include a heterogenous population of cells that include tumor-associated macrophages (TAMs). TAMs are major players in inducing the immunosuppressive microenvironment associated with many tumors. These lesions
Mitochondrial stress delays tumorigenesis in a Li-Fraumeni syndrome mouse model
Matthew P. Donnelly1, Jie Li1 and Paul M. Hwang1
As a prominent hub of metabolic activity, the mitochondrion can initiate retrograde signaling in response to bioenergetic stress that is important for various adaptive changes including cell cycle regulation [1][2].
Mitochondria organize the cellular proteostatic response and promote cellular senescence
Yanjun Li1, Lei Liu2, Yushan Zhu1 and Quan Chen1,2
Timely disposal and degradation of misfolded proteins and their aggregates is critical for cellular proteostasis and the well-being of a cell. During evolution, cells have acquired a sophisticated system to
Could de-stressing the brain be the solution for long-term weight loss?
Florian Seyfried1 and Mohammed K. Hankir2
INTRODUCTION One just needs to take a look at a typical vending machine (often found in hospitals) to appreciate what has happened to our food and drink. The relatively sudden