Publications de Daniel Constam

M6A methylation inhibits recruitment of the Dand5 3’UTR to the left-right determinant Bicc1

Daniel Constam, Benjamin Marcel Daniel Rothé, Simon Fortier

In vertebrates, left-right (LR) asymmetry is specified by asymmetric decay of Dand5 messenger RNA (mRNA) mediated by the recruitment of the BicC family RNA binding protein 1 (Bicc1). Besides regulating organ laterality, Bicc1 is required to prevent cystic ...

Cold Spring Harbor Laboratory2025

Kallikrein-8 mediates furin-independent Activin-A precursor processing to stimulate tumor growth in melanoma

Daniel Constam, Nadine Fournier, Céline Emmanuelle Schmuziger, Manon Bulliard, Katarina Pinjusic

Receptor binding of TGF-β and related ligands such as Activin-A requires cleavage of a furin site in their dimeric precursor proteins. Melanoma cells cleave one Activin-A subunit independently of furin and related proprotein convertases, raising questions ...

2025

Inhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING

Christian Iseli, Nicolas Jean Philippe Guex, Daniel Constam, Giovanna Ambrosini, Katarina Pinjusic

The transforming growth factor-beta (TGF-beta) family member activin A (hereafter Activin-A) is overexpressed in many cancer types, often correlating with cancer-associated cachexia and poor prognosis. Activin-A secretion by melanoma cells indirectly imped ...

Frontiers Media Sa2024

Stepwise release of Activin-A from its inhibitory prodomain is modulated by cysteines and requires furin coexpression to promote melanoma growth

Daniel Constam, Pierpaolo Ginefra, Hatice Altug, Benjamin Marcel Daniel Rothé, Céline Emmanuelle Schmuziger, Manon Bulliard, Katarina Pinjusic, Saeid Ansaryan

The Activin-A precursor dimer can be cleaved by furin, but how this proteolytic maturation is regulated in vivo and how it facilitates access to signaling receptors is unclear. Here, analysis in a syngeneic melanoma grafting model shows that without furin ...

2024

Bicc1 ribonucleoprotein complexes specifying organ laterality are licensed by ANKS6-induced structural remodeling of associated ANKS3

Daniel Constam, Matteo Dal Peraro, Benjamin Marcel Daniel Rothé, Simon Fortier, Zhidian Zhang

Organ laterality of vertebrates is specified by accelerated asymmetric decay of Dand5 mRNA mediated by Bicaudal-C1 (Bicc1) on the left side, but whether binding of this or any other mRNA to Bicc1 can be regulated is unknown. Here, we found that a CRISPR-en ...

PUBLIC LIBRARY SCIENCE2023

Antagonistic interactions among structured domains in the multivalent Bicc1-ANKS3-ANKS6 protein network govern phase transitioning of target mRNAs

Daniel Constam, Benjamin Marcel Daniel Rothé, Céline Emmanuelle Schmuziger, Simon Fortier, Céline Gagnieux

The growing number of diseases linked to aberrant phase transitioning of ribonucleoproteins highlights the need to uncover how the interplay between multivalent protein and RNA interactions is regulated. Cytoplasmic granules of the RNA binding protein Bica ...

CELL PRESS2023

Activin-A impairs CD8 T cell-mediated immunity and immune checkpoint therapy response in melanoma

Daniel Constam, Etienne Meylan, Julien Robert Rémi Faget, Olivier Andreas Dubey, Katarina Pinjusic

Background Activin-A, a transforming growth factor beta family member, is secreted by many cancer types and is often associated with poor disease prognosis. Previous studies have shown that Activin-A expression can promote cancer progression and reduce the ...

BMJ PUBLISHING GROUP2022

Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex

Daniel Constam, Benjamin Marcel Daniel Rothé

Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examin ...

Nature Portfolio2021

Time-Resolved Scanning Ion Conductance Microscopy for Three-Dimensional Tracking of Nanoscale Cell Surface Dynamics

Aleksandra Radenovic, Daniel Constam, Georg Fantner, Adrian Pascal Nievergelt, Samuel Mendes Leitão, Alexandre Louis André Persat, Xavier Jean-Yves Pierrat, Katarina Pinjusic, Barney Frederick Drake, Vytautas Navikas, Charlène Cécile Geneviève Brillard

Nanocharacterization plays a vital role in understanding the complex nanoscale organization of cells and organelles. Understanding cellular function requires high-resolution information about how the cellular structures evolve over time. A number of techni ...

AMER CHEMICAL SOC2021

Role of the RNA-binding protein Bicaudal-C1 and interacting factors in cystic kidney diseases

Daniel Constam, Lucía Carolina Leal Esteban, Benjamin Marcel Daniel Rothé, Céline Gagnieux

Polycystic kidneys frequently associate with mutations in individual components of cilia, basal bodies or centriolar satellites that perturb complex protein networks. In this review, we focus on the RNA-binding protein Bicaudal-C1 (BICC1) which was found m ...

2020

Comment on "Human dignity and gene editing"

Daniel Constam

WILEY2019

A novel cell-based sensor detecting the activity of individual basic proprotein convertases

Daniel Constam, Karin Irmgard Löw, Stefan Kunz

The basic proprotein convertases (PCs) furin, PC1/3, PC2, PC5/6, PACE4, PC4, and PC7 are promising drug targets for human diseases. However, developing selective inhibitors remains challenging due to overlapping substrate recognition motifs and limited str ...

WILEY2019

Compartment-Specific Biosensors Reveal a Complementary Subcellular Distribution of Bioactive Furin and PC7

Daniel Constam, Prudence Jane Donovan, Pierpaolo Ginefra, Sylvain Frédéric Bessonnard

2018

Crystal Structure of Bicc1 SAM Polymer and Mapping of Interactions between the Ciliopathy-Associated Proteins Bicc1, ANKS3, and ANKS6

Daniel Constam, Lucía Carolina Leal Esteban, Benjamin Marcel Daniel Rothé, Simon Fortier, Manuela Isenschmid

2018

Role of Bicaudal C1 in renal gluconeogenesis and its novel interaction with the CTLH complex

Daniel Constam, Lucía Carolina Leal Esteban, Benjamin Marcel Daniel Rothé, Simon Fortier, Manuela Isenschmid

2018

Paracrine Activin-A Signaling Promotes Melanoma Growth and Metastasis through Immune Evasion

Daniel Constam, Susanna Eveliina Kallioinen, Olivier Andreas Dubey, Patrick Mueller

The secreted growth factor Activin-A of the transforming growth factor beta family and its receptors can promote or inhibit several cancer hallmarks including tumor cell proliferation and differentiation, vascularization, lymphangiogenesis and inflammation ...

2017

Epiblast-specific loss of HCF-1 leads to failure in anterior-posterior axis specification

Daniel Constam, Winship Herr, Sylvain Frédéric Bessonnard

Mammalian Host-Cell Factor 1 (HCF-1), a transcriptional co-regulator, plays important roles during the cell-division cycle in cell culture, embryogenesis as well as adult tissue. In mice, HCF-1 is encoded by the X-chromosome-linked Hcfc1 gene. Induced Hcfc ...

Academic Press Inc Elsevier Science2016

Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA

Daniel Constam, Séverine Marguerite Urfer, Florian Urs Bernet, Lucía Carolina Leal Esteban, Benjamin Marcel Daniel Rothé

Loss of the RNA-binding protein Bicaudal-C (Bicc1) provokes renal and pancreatic cysts as well as ectopic Wnt/beta-catenin signaling during visceral left-right patterning. Renal cysts are linked to defective silencing of Bicc1 target mRNAs, including adeny ...

American Society for Microbiology2015

Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

Daniel Constam, Anne Grapin-Botton, Joan Goulley, Laurence Anne E Lemaire, Jacques Rougemont, Yung Hae Kim

In human, mutations in bicaudal C1 (BICC1), an RNA binding protein, have been identified in patients with kidney dysplasia. Deletion of Bicc1 in mouse leads to left-right asymmetry randomization and renal cysts. Here, we show that BICC1 is also expressed i ...

Company Of Biologists Ltd2015

ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm

Daniel Constam

The secreted glycoprotein sonic hedgehog (Shh) is expressed in the prechordal mesoderm, where it plays a crucial role in induction and patterning of the ventral forebrain. Currently little is known about how Shh is regulated in prechordal tissue. Here we s ...

Company of Biologists2015