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

Metabolic and functional reprogramming of myeloid-derived suppressor cells and their therapeutic control in glioblastoma

Woong-Jai Won1, Jessy S. Deshane2, Jianmei W. Leavenworth3, Claudia R. Oliva4 and Corinne E. Griguer4

Glioblastoma, also known as glioblastoma multiforme, is the most common and deadliest form of high-grade malignant brain tumors with limited available treatments. Within the glioblastoma tumor microenvironment (TME), tumor cells, stromal cells, and infiltrating immune cells continuously interact and exchange signals through various secreted factors including cytokines, chemokines, growth factors, and metabolites. Simultaneously, they dynamically reprogram their metabolism according to environmental energy demands such as hypoxia and neo-vascularization. Such metabolic reprogramming can determine fates and functions of tumor cells as well as immune cells. Ultimately, glioma cells in the TME transform immune cells to suppress anti-tumor immune cells such as T, natural killer (NK) cells, and dendritic cells (DC), and evade immune surveillance, and even to promote (...)

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

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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

Regulation of T cell antitumor immune response by tumor induced metabolic stress

Fanny Chalmin1,2,3,4, Mélanie Bruchard1,2,3,4, Frederique Vegran1,2,3,4 and Francois Ghiringhelli1,2,3,4

Adaptive T cell immune response is essential for tumor growth control. The efficacy of immune checkpoint inhibitors is regulated by intratumoral immune response. The tumor microenvironment has a major role in adaptive immune response tuning. Tumor cells generate a particular metabolic environment in comparison to other tissues. Tumors are characterized by glycolysis, hypoxia, acidosis, amino acid depletion and fatty acid metabolism modification. Such metabolic changes promote tumor growth, impair immune response and lead to resistance to therapies. This review will detail how these modifications strongly affect CD8 and CD4 T cell functions and impact immunotherapy efficacy.

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Regulation of T cell antitumor immune response by tumor induced metabolic stress

Fanny Chalmin1,2,3,4, Mélanie Bruchard1,2,3,4, Frederique Vegran1,2,3,4 and Francois Ghiringhelli1,2,3,4

Adaptive T cell immune response is essential for tumor growth control. The efficacy of immune checkpoint inhibitors is regulated by intratumoral immune response. The tumor microenvironment has a major role in adaptive immune response tuning. Tumor cells generate a particular metabolic environment in comparison to other tissues. Tumors are characterized by glycolysis, hypoxia, acidosis, amino acid depletion and fatty acid metabolism modification. Such metabolic changes promote tumor growth, impair immune response and lead to resistance to therapies. This review will detail how these modifications strongly affect CD8 and CD4 T cell functions and impact immunotherapy efficacy.

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