JIP1 binding to RBP-Jk mediates cross-talk between the Notch1 and JIP1-JNK signaling pathway.
Notch1 signaling has a critical function in maintaining a balance among cell proliferation, differentiation, and apoptosis. Our earlier work showed that the Notch1 intracellular domain interferes with the scaffolding function of c-Jun N-terminal kinase (JNK)-interacting protein-1 (JIP1), yet the effect of JIP1 for Notch1-recombining binding protein suppressor of hairless (RBP-Jk) signaling remains unknown. Here, we show that JIP1 suppresses Notch1 activity. JIP1 was found to physically associate with either intracellular domain of Notch1 or RBP-Jk and interfere with the interaction between them. Furthermore, we ascertained that JIP1 caused the cytoplasmic retention of RBP-Jk through an interaction between the C-terminal region of JIP1 including Src homology 3 domain and the proline-rich domain of RBP-Jk. We also found that RBP-Jk inhibits JIP1-mediated activation of the JNK1 signaling cascade and cell death. Our results suggest that direct protein-protein interactions coordinate cross-talk between the Notch1-RBP-Jk and JIP1-JNK pathways.
Kim
M-Y
MY
Hormone Research Center, Chonnam National University, Gwangju, Republic of Korea.
Ann
E-J
EJ
Mo
J-S
JS
Dajas-Bailador
F
F
Seo
M-S
MS
Hong
J-A
JA
Jung
J
J
Choi
Y-H
YH
Yoon
J-H
JH
Kim
S-M
SM
Choi
E-J
EJ
Hoe
H-S
HS
Whitmarsh
A J
AJ
Park
H-S
HS
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051381:Rats; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D036341:Intercellular Signaling Peptides and Proteins; C490665:Mapk8ip protein, mouse; D008565:Membrane Proteins; D051881:Receptor, Notch1; D011994:Recombinant Proteins; D048031:JNK Mitogen-Activated Protein Kinases