As binding of WD40 repeats of FBXW7 requires conserved phosphodegron in the PEST domain of NICD1, especially phosphorylation of threonine residue T2511 and serine residue S2513, FBXW7 cannot bind NICD1 PEST domain mutants which lack the conserved phosphodegron due to truncation of the PEST domain, or are not phosphorylated on conserved threonine and serine residues due to point mutations. Inability to bind FBXW7 and undergo FBXW7-mediated ubiquitination and degradation prolongs the half-life of NICD1 PEST domain mutants and results in persistent NOTCH1 signaling (O'Neil et al. 2007, Thompson et al. 2007).
Basso, G, Sulis, ML, Buonamici, S, Thompson, BJ, Aifantis, I, Palomero, T, Vilimas, T, Ferrando, AA
Draetta, G, Rao, S, Sears, R, Strack, P, Tibbitts, D, Hardwick, J, Pieters, R, Look, AT, Welcker, M, Meijerink, JP, Winter, C, Grim, J, O'Neil, J, Clurman, BE
Loss of function of p-NICD1 PEST domain mutants [nucleoplasm]
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