User:Apolena Zounarová/Sandbox 2

NOTCH1 is a member of NOTCH family receptor proteins which consists of four members (NOTCH1-4). NOTCH proteins are evolutionarily highly conserved signalling proteins responsible for direct transduction of developmental signals at the cell surface into change in a transcriptional profile in the nucleus.

Structure and Function of Notch1

NOTCH receptors are class I transmembrane glycoproteins composed of an extracellular subunit and transmembrane and intracellular subunit, which interact via a specialised heterodimerization domain (HD). The extracellular subunit engages ligand via several EGF-like repeats and further contains three LIN-12/NOTCH repeats (LNR) which stabilise the dimerization domain by holding the two NOTCH subunits together. The transmembrane-intracellular subunit contains a short extracellular juxtamembrane peptide, transmembrane sequence and cytoplasmic domains including RAM domain, nuclear localization signals (NLS), a series of ankyrin repeats, glutamine-rich region (OPA) and C-terminal PEST domain which serves as a ligand-activated transcription factor ^[1].

Proteolytic Events During Notch1 Secretion and Signal Transduction

Furin-type Convertase Cleavage

Additional Cleavages in Response to Receptor Activation

Heterodimerization Domain and Negative Regulatory Region

T-cell Acute Lymphoblastic Leukaemia

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Structural highlights

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