Question

Phosphorylation-dependent binding of F-box protein B-TrCP containing E3 ubiquitin ligase to human WEE1A. S123 is phosphorylated by a CDK and the phosphorylation primes CK2 to phosphorylate S121 resulting in creation of a B-TCP phosphodegron (EEGFGpS121) that is responsible for the instability of WEE1A during interphase. At the onset of M-phase, when activated Plk1 accumulates, Plk1 binds to WEE1A to the PBD binding motif surrounding PS123 (SpSP) via its PBD and phosphorylates S53 resulting in generation of the second phosphodegron (DpSAFQE). These two phosphodegrons act cooperatively to promote B-TCP binding and the turnover of Wee1A, PLK1 (PBD binding) CK2 Cdc2 Wee1A DSAFQE T2T 123 EEGFGSSSPVK protein kinase domain B-TCP Binding consensus: DpSGXXpS Rbx1 Skpl Cult

Answer 1

The role of the E3 ubiquitin ligase in Wee-1 regulation is Wee-1 kinase activity inactivates E3 ubiquitin ligase at series 123 causing degradation of ubiquitin and passage through the cycle.