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
Stress granules regulate paraspeckles: RNP granule continuum at work
Haiyan An1 and Tatyana A. Shelkovnikova1
Eukaryotic cells contain a variety of large, multicomponent RNA-protein complexes termed ribonucleoprotein (RNP) granules. RNP granules represent membraneless organelles – biomolecular condensates lacking a membrane and maintained through an intricate
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
Endoplasmic reticulum and Golgi stress in microcephaly
Sandrine Passemard1,2, Franck Perez3, Pierre Gressens1,4 and Vincent El Ghouzzi1
Microcephaly is a neurodevelopmental condition characterized by a small brain size associated with intellectual deficiency in most cases and is one of the most frequent clinical sign encountered in neurodevelopmental disorders. It can result from a wide range of environmental insults occurring during pregnancy or postnatally, as well as from various genetic causes and represents a highly heterogeneous condition. However, several lines of evidence highlight a compromised mode of division of the cortical precursor cells during neurogenesis, affecting neural commitment or survival as one of the common mechanisms leading to a limited production of neurons and associated with the most severe forms of congenital microcephaly. In this context, the emergence of the endoplasmic reticulum (ER) and the Golgi apparatus as key guardians of cellular homeostasis, especially through the regulation of proteostasis, has raised the hypothesis that pathological ER and/or Golgi stress could contribute significantly to cortical impairments eliciting microcephaly. In (…)
LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects
Hsin-Wei Liao1,#, Christopher Garris1,#, Christina Pfirschke1, Steffen Rickelt2, Sean Arlauckas1, Marie Siwicki1, Rainer H. Kohler1, Ralph Weissleder1, Vibeke Sundvold-Gjerstad3, Baldur Sveinbjørnsson3,4, Øystein Rekdal3,4 and Mikael J. Pittet1
LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in phase II clinical trials. Here we aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer that typically resist current treatment options and to better understand the drug’s mode of action in vivo. We report LTX-315 mediates profound antitumor effects against Braf- and Pten-driven melanoma and delays the progression of Kras- and P53-driven soft tissue sarcoma in mice. Additionally, we show in melanoma that LTX-315 triggers two sequential phases of antitumor response. The first phase of response, which begins within minutes of drug delivery into tumors, is defined by disrupted tumor vasculature and decreased tumor burden and occurs independently of (...)
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 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