As NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain m...

created [InstanceEdit:2894855] Orlic-Milacic, M, 2013-01-02
dbId 2894856
displayName As NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain m...
modified [InstanceEdit:2982610] Orlic-Milacic, M, 2013-01-14
schemaClass Summation
text As NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain mutants are expected to behave as the wild-type NOTCH1 with respect to ligand binding and proteolytic cleavage mediated activation of signaling. However, once the NICD1 fragment of NOTCH1 is released, PEST domain mutations prolong its half-life and transcriptional activity through interference with FBXW7 (FBW7)-mediated ubiquitination and degradation of NICD1 (Weng et al. 2004, Thompson et al. 2007, O'Neil et al. 2007). All NOTCH1 PEST domain mutants annotated here (NOTCH1 Q2395*, NOTCH1 Q2440*, NOTCH1 P2474Afs*4 and NOTCH1 P2514Rfs*4) either have a truncated PEST domain or lack the PEST domain completely.
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