Reassembly of JIP1 Scaffold Complex in JNK MAP Kinase Pathway Using Heterologous Protein Interactions
Overview
Authors
Affiliations
Formation of signaling protein complexes is crucial for proper signal transduction. Scaffold proteins in MAP kinase pathways are thought to facilitate complex assembly, thereby promoting efficient and specific signaling. To elucidate the assembly mechanism of scaffold complexes in mammals, we attempted to rationally rewire JIP1-dependent JNK MAP kinase pathway via alternative assembly of JIP1 complex. When JIP1-JNK docking interaction in the complex was replaced with heterologous protein interaction domains, such as PDZ domains and JNK-binding domains, a functional scaffold complex was reconstituted, and JNK signaling was rescued. Reassembly of JIP1 complex using heterologous protein interactions was sufficient for restoring of JNK MAP kinase pathway to induce signaling responses, including JNK activation and cell death. These results suggest a simple yet modular mechanism for JIP1 scaffold assembly in mammals.
CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy.
Dong Y, Jin Q, Sun M, Qi D, Qu H, Wang X J Exp Clin Cancer Res. 2023; 42(1):68.
PMID: 36935496 PMC: 10026481. DOI: 10.1186/s13046-023-02644-x.
Speltz E, Zalatan J Biochemistry. 2020; 59(23):2182-2193.
PMID: 32433869 PMC: 7328773. DOI: 10.1021/acs.biochem.0c00205.
Compromised global embryonic transcriptome associated with advanced maternal age.
McCallie B, Parks J, Trahan G, Jones K, Coate B, Griffin D J Assist Reprod Genet. 2019; 36(5):915-924.
PMID: 31025158 PMC: 6541584. DOI: 10.1007/s10815-019-01438-5.
New insights into the structural dynamics of the kinase JNK3.
Mishra P, Gunther S Sci Rep. 2018; 8(1):9435.
PMID: 29930333 PMC: 6013471. DOI: 10.1038/s41598-018-27867-3.
C Robitaille A, Caron E, Zucchini N, Mukawera E, Adam D, Mariani M Sci Rep. 2017; 7(1):17388.
PMID: 29234123 PMC: 5727028. DOI: 10.1038/s41598-017-17689-0.