Mustapha Oulad-Abdelghani
University of Strasbourg
PhosphorylationTransduction (genetics)GastrulationDNA damageGeneral transcription factorTranslation (biology)Molecular biologyAntibodyNeuroscienceTranscription factor II DChemistryPhage displayEpitopeNeurodegenerationC9orf72TretinoinAtaxiaRetinoic acidPhosphorylated Histone H2AXHistone H2AXC9orf72 ProteinProgrammed cell deathTranscription (biology)Amyloid precursor protein secretaseRecombinant DNAAlzheimer's diseaseMonoclonal antibodyGeneticsDNABiochemistryCell growthRNA polymerase IIHistoneDNA replicationChromatinNucleosomeBiologyUntranslated regionCell biologyCancer cell
27Publications
17H-index
2,212Citations
Publications 27
Newest
#1Eric MoeglinH-Index: 2
#2Dominique DesplancqH-Index: 12
view all 14 authors...
Histone H2AX phosphorylated at serine 139 (γ-H2AX) is a hallmark of DNA damage, signaling the presence of DNA double-strand breaks and global replication stress in mammalian cells. While γ-H2AX can be visualized with antibodies in fixed cells, its detection in living cells was so far not possible. Here, we used immune libraries and phage display to isolate nanobodies that specifically bind to γ-H2AX. We solved the crystal structure of the most soluble nanobody in complex with the phosphopeptide ...
Source
#1Manon Boivin (UDS: University of Strasbourg)H-Index: 2
#2Jianwen Deng (PKU: Peking University)H-Index: 4
Last. Nicolas Charlet-Berguerand (UDS: University of Strasbourg)H-Index: 25
view all 20 authors...
Summary Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by the presence of intranuclear inclusions of unknown origin. NIID is caused by an expansion of GGC repeats in the 5′ UTR of the NOTCH2NLC (N2C) gene. We found that these repeats are embedded in a small upstream open reading frame (uORF) (uN2C), resulting in their translation into a polyglycine-containing protein, uN2CpolyG. This protein accumulates in intranuclear inclusions in cell and mouse mod...
3 CitationsSource
#1Yujing Gao (University of Melbourne)H-Index: 4
#2Gabrielle R. Wilson (University of Melbourne)H-Index: 11
Last. Paul J. Lockhart (University of Melbourne)H-Index: 47
view all 10 authors...
Pathogenic variants in the gene encoding the small GTPase Ras analogue in Brain 39b (RAB39B) are associated with early-onset parkinsonism. In this study we investigated the expression and localization of RAB39B (RNA and protein) in mouse brain tissue to gain a better understanding of its normal physiological function(s) and role in disease.We developed novel resources, including monoclonal antibodies directed against RAB39B and mice with Rab39b knockout, and performed real-time PCR and western b...
5 CitationsSource
#1Eric Moeglin (UDS: University of Strasbourg)H-Index: 2
#2Dominique Desplancq (UDS: University of Strasbourg)H-Index: 12
Last. Etienne Weiss (UDS: University of Strasbourg)H-Index: 25
view all 10 authors...
Phosphorylated histone H2AX (γ-H2AX), a central player in the DNA damage response (DDR), serves as a biomarker of DNA double-strand break repair. Although DNA damage is generally visualized by the formation of γ-H2AX foci in injured nuclei, it is unclear whether the widespread uniform nuclear γ-H2AX (called pan-nuclear) pattern occurring upon intense replication stress (RS) is linked to DDR. Using a novel monoclonal antibody that binds exclusively to the phosphorylated C-terminus of H2AX, we dem...
28 CitationsSource
#1Petra Frick (German Center for Neurodegenerative Diseases)H-Index: 4
#2Chantal Sellier (UDS: University of Strasbourg)H-Index: 20
Last. Manuela Neumann (University of Tübingen)H-Index: 82
view all 13 authors...
Hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, but the pathogenic mechanism of this mutation remains unresolved. Haploinsufficiency has been proposed as one potential mechanism. However, insights if and how reduced C9orf72 proteins levels might contribute to disease pathogenesis are still limited because C9orf72 expression, localization and functions in the central nervous system (CNS) are uncertain, in pa...
52 CitationsSource
#1Sascha ConicH-Index: 5
#2Dominique DesplancqH-Index: 12
Last. Laszlo ToraH-Index: 81
view all 13 authors...
Fluorescent labeling of endogenous proteins for live-cell imaging without exogenous expression of tagged proteins or genetic manipulations has not been routinely possible. We describe a simple versatile antibody-based imaging approach (VANIMA) for the precise localization and tracking of endogenous nuclear factors. Our protocol can be implemented in every laboratory allowing the efficient and nonharmful delivery of organic dye-conjugated antibodies, or antibody fragments, into different metazoan...
22 CitationsSource
#1Chantal Sellier (UDS: University of Strasbourg)H-Index: 20
#2Ronald A.M. Buijsen (EUR: Erasmus University Rotterdam)H-Index: 14
view all 28 authors...
Summary Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a limited expansion of CGG repeats in the 5′ UTR of FMR1 . Two mechanisms are proposed to cause FXTAS: RNA gain-of-function, where CGG RNA sequesters specific proteins, and translation of CGG repeats into a polyglycine-containing protein, FMRpolyG. Here we developed transgenic mice expressing CGG repeat RNA with or without FMRpolyG. Expression of FMRpolyG is pathogenic, while the sole expression...
124 CitationsSource
#1Chantal Sellier (UDS: University of Strasbourg)H-Index: 20
#2Maria-Letizia Campanari (French Institute of Health and Medical Research)H-Index: 7
Last. Nicolas Charlet-Berguerand (UDS: University of Strasbourg)H-Index: 25
view all 11 authors...
Abstract An intronic expansion of GGGGCC repeats within the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS‐FTD). Ataxin‐2 with intermediate length of polyglutamine expansions (Ataxin‐2 Q30x) is a genetic modifier of the disease. Here, we found that C9ORF72 forms a complex with the WDR41 and SMCR8 proteins to act as a GDP/GTP exchange factor for RAB8a and RAB39b and to thereby control autophagic flux. Depletion of C9orf72 in neurons...
237 CitationsSource
#1Dominique Desplancq (UDS: University of Strasbourg)H-Index: 12
#2Guillaume Freund (UDS: University of Strasbourg)H-Index: 4
Last. Etienne Weiss (UDS: University of Strasbourg)H-Index: 25
view all 13 authors...
Although chemical inhibition of the DNA damage response (DDR) in cancer cells triggers cell death, it is not clear if the fork blockade achieved with inhibitors that neutralise proteins of the replisome is sufficient on its own to overcome the DDR. Monoclonal antibodies to PCNA, which block the DNA elongation process in vitro, have been developed. When these antibodies were transduced into cancer cells, they are able to inhibit the incorporation of nucleoside analogues. When co-delivered with an...
16 CitationsSource
#1Etienne Schaeffer (UDS: University of Strasbourg)H-Index: 3
#2Marc Vigneron (UDS: University of Strasbourg)H-Index: 17
Last. Mariel Donzeau (UDS: University of Strasbourg)H-Index: 5
view all 6 authors...
The transcription factor ATF7 undergoes multiple post-translational modifications, each of which has distinct effects upon ATF7 function. Here, we show that ATF7 phosphorylation on residue Thr112 exclusively occurs during mitosis, and that ATF7 is excluded from the condensed chromatin. Both processes are CDK1/cyclin B dependent. Using a transduced neutralizing monoclonal antibody directed against the Thr112 epitope in living cells, we could demonstrate that Thr112 phosphorylation protects endoge...
3 CitationsSource