Publications by 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, Manon Bulliard, Céline Emmanuelle Schmuziger, 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

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

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

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

Matteo Dal Peraro, Daniel Constam, 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, Simon Fortier, Céline Gagnieux, Céline Emmanuelle Schmuziger

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, Georg Fantner, Daniel Constam, Alexandre Louis André Persat, Barney Frederick Drake, Adrian Pascal Nievergelt, Vytautas Navikas, Samuel Mendes Leitão, Xavier Jean-Yves Pierrat, 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, Benjamin Marcel Daniel Rothé, Lucía Carolina Leal Esteban, 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