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 impact of endothelial cell death in the brain and its role after stroke: A systematic review
Marietta Zille1, Maulana Ikhsan1, Yun Jiang1,2, Josephine Lampe1,2, Jan Wenzel1,2 and
Markus Schwaninger1,2
INTRODUCTION The brain is a metabolically active organ that consumes about 20% of the total energy of the body [1]. At the same time, it is unable to store significant
Inflammation induced PD-L1-specific T cells
Shamaila Munir1, Mia Thorup Lundsager1, Mia Aabroe Jørgensen1, Morten Hansen1, Trine Hilkjær Petersen2, Charlotte Menne Bonefeld2, Christina Friese1, Özcan Met1,2, Per thor Straten1,2 and Mads Hald Andersen1,2,3
PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both (…)
Gold Nanoparticles sensitize pancreatic cancer cells to gemcitabine
Yanyan Huai1, Yushan Zhang1, Xunhao Xiong1, Shamik Das2, Resham Bhattacharya2 and Priyabrata Mukherjee1,2
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. The mortality rate closely parallels that of incidence [1][2]. The current standard of care for advanced stage PDAC patients includes
Unraveling the molecular principles by which ceramides commit cells to death
Shashank Dadsena1, Dina G. Hassan1 and Joost C.M. Holthuis1
EMERGENCE OF CERAMIDES AS TUMOR SUPPRESSOR LIPIDS Sphingolipids are unusually versatile membrane components that participate in mechanical stability, signaling, and molecular sorting. As the path to their production is paved
Immunosurveillance of cancer cell stress
Seila Lorenzo-Herrero1-3, Christian Sordo-Bahamonde1-3, Segundo González1-3 and Alejandro López-Soto1-3
Cancer development is tightly controlled by effector immune responses that recognize and eliminate malignantly transformed cells. Nonetheless, certain immune subsets, such as tumor-associated macrophages, have been described to promote tumor growth, unraveling a double-edge role of the immune system in cancer. Cell stress can modulate the crosstalk between immune cells and tumor cells, reshaping tumor immunogenicity and/or immune function and phenotype. Infiltrating immune cells are exposed to the challenging conditions typically present in the tumor microenvironment. In return, the myriad of signaling pathways activated in response to stress conditions may tip the balance toward stimulation of antitumor responses or immune-mediated tumor progression. Here, we explore how distinct situations of cellular stress influence innate and adaptive immunity and the consequent impact on cancer establishment and progression.
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
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
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
Serum- and glucocorticoid-inducible kinase 1 and the response to cell stress
Florian Lang1, Christos Stournaras2, Nefeli Zacharopoulou2, Jakob Voelkl3,4, Ioana Alesutan3,4,5
INTRODUCTION The ubiquitously expressed [1][2][3][4] serum- and glucocorticoid-inducible kinase 1 (SGK1) has originally been cloned as a gene up-regulated by serum and glucocorticoids in rat mammary tumor cells [1][5]. 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