Publications by authors named "Alexandre P Martin"
Notch proteins undergo ligand-induced proteolysis to release a nuclear effector that influences a wide range of cellular processes by regulating transcription. Despite years of study, however, how Notch induces the transcription of its target genes remains unclear. Here, we comprehensively examine the response to human Notch1 across a time course of activation using high-resolution genomic assays of chromatin accessibility and nascent RNA production.
View Article and Find Full Text PDFNotch proteins undergo ligand-induced proteolysis to release a nuclear effector that influences a wide range of cellular processes by regulating transcription. Despite years of study, however, how Notch induces the transcription of its target genes remains unclear. Here, we comprehensively examined the response to human Notch1 across a time course of activation using high-resolution genomic assays of chromatin accessibility and nascent RNA production.
View Article and Find Full Text PDFArticle Synopsis
- Mammalian Notch signaling is initiated when Delta or Jagged proteins bind to the Notch receptor, leading to the release of the Notch intracellular domain (NICD) that influences gene expression in the nucleus.
- Researchers used fluorescent tagging to observe the interactions between Notch and Delta in real-time as they interacted between sender and receiver cells after contact.
- The study revealed that Notch and Delta formed synapses quickly, with a peak NICD accumulation in the nucleus of the receiver cell after about 45 minutes, highlighting the precise timing and sequence of events in Notch signaling.
Article Synopsis
- Notch signaling in mammals is activated when Delta or Jagged proteins bind to Notch, leading to the release of the Notch intracellular domain (NICD) which then regulates gene expression in the nucleus.
- Researchers fluorescently tagged Notch and Delta to study their interactions, finding that both proteins rapidly joined together at cell contact sites, forming synapses that peaked at a 1:1 ratio.
- The study revealed that the formation of these synapses occurs before NICD enters the nucleus, with NICD levels peaking around 45 minutes post-contact, highlighting a precise timing relationship between Notch-Delta interactions and NICD production.
Article Synopsis
- Notch signaling is crucial for cell fate decisions, involving the cleavage of the Notch receptor to release its active intracellular domain (NICD) that promotes gene transcription in the nucleus.
- The process begins when a ligand binds to Notch, triggering its cleavage by proteases ADAM10 and γ-secretase, leading to NICD's translocation to the nucleus.
- Using advanced mass spectrometry, researchers mapped the timing and location of Notch's cleavage and movement, revealing significant nuclear complex formation and enzymatic recruitment within 45 minutes after γ-secretase inhibition removal, highlighting potential targets for influencing Notch signaling.
The Hippo signal transduction pathway is an essential regulator of organ size during developmental growth by controlling multiple cellular processes such as cell proliferation, cell death, differentiation, and stemness. Dysfunctional Hippo signaling pathway leads to dramatic tissue overgrowth. Here, we will briefly introduce the Hippo tumor suppressor pathway before focusing on one of its members and the unexpected twists that followed our quest of its functions in its multifarious actions beside the Hippo pathway: the STK38 kinase.
View Article and Find Full Text PDFThe proper segregation of basic elements such as the compartmentalization of the genome and the shuttling of macromolecules between the nucleus and the cytoplasm is a crucial mechanism for homeostasis maintenance in eukaryotic cells. XPO1 (Exportin 1) is the major nuclear export receptor and is required for the export of proteins and RNAs out of the nucleus. STK38 (also known as NDR1) is a Hippo pathway serine/threonine kinase with multifarious functions in normal and cancer cells.
View Article and Find Full Text PDFSTK38 (also known as NDR1) is a Hippo pathway serine/threonine protein kinase with multifarious functions in normal and cancer cells. Using a context-dependent proximity-labeling assay, we identify more than 250 partners of STK38 and find that STK38 modulates its partnership depending on the cellular context by increasing its association with cytoplasmic proteins upon nutrient starvation-induced autophagy and with nuclear ones during ECM detachment. We show that STK38 shuttles between the nucleus and the cytoplasm and that its nuclear exit depends on both XPO1 (aka exportin-1, CRM1) and STK38 kinase activity.
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