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Cell Signaling. Lecture 13 and 14. Ligand -activated Notch undergoes 2 cleavages before releasing the transcription factor. ADAM10: A disintegrin and Metalloprotease.
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Cell Signaling Lecture 13 and 14
Ligand-activated Notch undergoes 2 cleavages before releasing the transcription factor ADAM10: A disintegrin and Metalloprotease Notch is cleaved by the matrix metalloprotease ADAM10, which is bound to the membrane releasing the extracellular Notch segment Y-secretase, a complex of four membrane proteins including the protease presenilin 1 (PS1) then associates with the remaining portion of Notch and catalyzes an intramembrane cleavage that releases the cytosolic segment of Notch.
Wnt Signals trigger release of a transcription from cytosolic protein complex In the absence of Wnt(proto-oncogene: a normal cellular gene whose inappropriate expression promotesthe onset of cancer), B-catenin is found in a complex with Axin, APC and the kinase GSK3. The kinase GSK3 phosphorylates B-catenin leading to its degradation. The TCF transcription factor in the nucleus acts as a repressor of target genes unless altered by Wnt signaling.
Binding of Wnt to its receptor Frizzled (Fz) triggers phosphorylation of the LRP co-receptor by GSK3 and another and another kinase, and thus allows subsequent binding of Axin. This disrupts the Axin-APC-GSK3-B-catenin complex, preventing phosphorylation of B-catenin by GSK3 which leads accumulation of B-catenin in the cell. After translocation to the nucleus, B-catenin may act with TCF to activate target genes or, alternately cause the export of TCF from the nucleus and possibly its activation in the cytosol