AI Article Synopsis
- Many regulatory proteins, like c-Jun, are found in disordered regions that play key roles in cellular processes such as growth and response to signals.
- The stability of c-Jun is influenced by interactions with the E3 ubiquitin ligase SCF and the isomerase Pin1, which are not fully understood.
- Our research shows that phosphorylation of c-Jun is crucial for its strong interaction with Fbw7, and that Pin1 modifies c-Jun to impact its degradation, highlighting how weak binding regions can create strong regulatory interactions.
Article Abstract
Many regulatory proteins, including the transcription factor c-Jun, are highly enriched in disordered protein regions that govern growth, division, survival, differentiation, and response to signals. The stability of c-Jun is controlled by poorly understood regulatory interactions of its disordered region with both the E3 ubiquitin ligase SCF and prolyl cis-trans isomerase Pin1. We use nuclear magnetic resonance and fluorescence studies of c-Jun to demonstrate that multisite c-Jun phosphorylation is required for high-affinity interaction with Fbw7. We show that the Pin1 WW and PPIase domains interact in a dynamic complex with multiply phosphorylated c-Jun. Importantly, Pin1 isomerizes a pSer-Pro peptide bond at the c-Jun N terminus that affects binding to Fbw7 and thus modulates the ubiquitin-mediated degradation of c-Jun. Our findings support the general principle that multiple weak binding motifs within disordered regions can synergize to yield high-affinity interactions and provide rapidly evolvable means to build and fine-tune regulatory events.
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| http://dx.doi.org/10.1016/j.str.2017.11.003 | DOI Listing |
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