BIOcentre 

Lunaret Montpellier

Title : Passive Yet Essential, Polycomb Repression in Development and Disease
Contact : carla.heredia@igmm.cnrs.fr

CRBM External Seminar
“Machine Learning and Structure-Based Approaches for the Discovery of Biomarkers and Bioactive Compounds”
Contact: andrey.kajava@crbm.cnrs.fr

Title : “Epigenetic and cis-regulatory determinants of tumorigenesis »
Contact : nadine.laguette@igmm.cnrs.fr

Title: « Signal peptides as timing codes: regulating protein fate at the ER gate »
Contact : daniel.fisher@igmm.cnrs.fr 

The entry of secretory and membrane proteins into the endoplasmic reticulum (ER) is usually viewed as a rapid co-translational process driven by N-terminal signal peptides (SPs). We have uncovered that a subset of SPs can instead impose a delay at the ER gate, transiently exposing nascent proteins to the cytosol before their entry into the secretory pathway. This “delayed translocation” creates a regulatory window in which domains normally destined to become extracellular or luminal can acquire cytosolic modifications.
PD-L1 exemplifies this mechanism: its suboptimal SP delays ER entry and allows cytosolic regulation of its extracellular domain, shaping PD-L1 maturation, trafficking and function. Beyond revealing SPs as timing codes, this mechanism exposes SP-dependent vulnerabilities that can be exploited pharmacologically. Using two assays we developed, the cytoRUSH and the RELITE, we show that selective interference with Sec61-dependent translocation can be monitored and harnessed to identify small molecules that block PD-L1 ER entry and redirect it toward cytosolic degradation.

References :
Cannata Serio, M. et al. A delayed translocation into the endoplasmic reticulum controls the post-translational modifications of PD-L1. Nat Commun. 2026 Apr 11;  17(1): 5059.

Vitale, F. et al. A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression. Nat Commun. 2025 Aug 6;  16(1): 7243.

Title: The Genotype–Phenotype Relationship as Mediator of Therapy Resistance in Acute Myeloid Leukemia 

Abstract:
Acute myeloid leukemia (AML) is characterized by extensive genetic and phenotypic heterogeneity. Leukemic stem cells (LSCs) are a self-renewing subpopulation of AML cells that sustains disease initiation, progression, and relapse. By translating the underlying pathogenic genotype into a malignant cellular phenotype and generating the progeny that constitute the bulk of the leukemia, LSCs lie at the interface between genotype and phenotype. Over the past decade, both genetic alterations and cellular phenotypes have emerged as important determinants of therapeutic response in AML. Deciphering how these features interact within LSCs may therefore provide new insights into treatment response, disease persistence, and the development of therapy resistance.

Contact : guillaume.bossis@igmm.cnrs.fr