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Notch belongs to a family of transmembrane proteins that are widely conserved from flies to vertebrates and are thought to be involved in cell-fate decisions. In Drosophila, the Suppressor of hairless (Su(H)) gene and genes of the Enhancer of split (E(Spl)) complex, which encode proteins of the basic helix-loop-helix type have been implicated in the Notch(More)
We have previously reported the presence of a hormone-inducible transcriptional activation function (TAF-2) within the region of the estrogen receptor (ER) that contains the hormone binding domain. We show here that the N-terminal A/B region of the ER contains an independent constitutive activation function (TAF-1) that exhibits cell type specificity since(More)
Serotonin (5-HT) has provided a useful tool to study plasticity of nociceptive sensory neurons in Aplysia. Because noxious stimulation causes release of 5-HT and long-term hyperexcitability (LTH) of sensory neuron somata and because 5-HT treatment can induce long-term synaptic facilitation of sensory neuron synapses, a plausible hypothesis is that 5-HT also(More)
The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the(More)
ctivation of mammalian Notch receptor by its ligands induces TNF ␣-converting enzyme–dependent ecto-domain shedding, followed by intramembrane proteo-lysis due to presenilin (PS)-dependent ␥-secretase activity. Here, we demonstrate that a new modification, a mono-ubiquitination, as well as clathrin-dependent endocytosis, is required for ␥-secretase(More)
We showed previously that coactivators mediating stimulation by different activators were associated with the TATA-binding protein (TBP) in distinct TFIID complexes. We have characterized a human TBP-associated factor (TAF), hTAFII30, associated with a subset of TFIID complexes. hTAFII30 interacts with the AF-2-containing region E of the human estrogen(More)
BACKGROUND The regulation of Notch signaling heavily relies on ubiquitination events. Drosophila Su(dx), a member of the HECT family of ubiquitin-ligases, has been described as a negative regulator of Notch signaling, acting on the post-endocytic sorting of Notch. The mammalian ortholog of Su(dx), Itch/AIP4, has been shown to have multiple substrates,(More)
Activation of the mammalian Notch receptor after ligand binding relies on a succession of events including metalloprotease-cleavage, endocytosis, monoubiquitination, and eventually processing by the gamma-secretase, giving rise to a soluble, transcriptionally active molecule. The Notch1 receptor was proposed to be monoubiquitinated before its(More)
The estrogen receptor (ER) contains two nonacidic transcriptional activation functions, AF-1 and AF-2 (formerly TAF-1 and TAF-2). In this study we show that AF-1 and AF-2 are able to stimulate transcription in vitro in a HeLa cell system when fused to the DNA binding domain of the yeast activator GAL4. We also demonstrate that a factor(s) required for the(More)
The very conserved Notch pathway is used iteratively during development and adulthood to regulate cell fates. Notch activation relies on interactions between neighboring cells, through the binding of Notch receptors to their ligands, both transmembrane molecules. This inter-cellular contact initiates a cascade of events eventually transforming the cell(More)