Splice variant-specific stabilization of JNKs by IB1/JIP1.
Islet-Brain 1 (IB1) (also called JNK-interacting protein 1; JIP1) is a scaffold protein that tethers components of the JNK mitogen-activated protein kinase pathway inducing a modulation of the activity and the target specificity of the JNK kinases. Dysfunctions in IB1 have been associated with diseases such as early type II diabetes. To gain more insight in the functions of IB1, its ability to modulate the expression levels of the various JNK proteins was assessed. Each of the three JNK genes gives rise to several splice variants encoding short or long proteins. The expression levels of the short JNK proteins, but not of the long variants, were systematically higher in rat tissues and in transformed cell lines expressing high IB1 levels compared to tissues and cells with no or low IB1 expression. HEK293 cells bearing a tetracycline-inducible IB1 construct showed a specific increase of the short JNK endogenous splice variants in the presence of tetracycline. The augmented expression level of the short JNK splice variants induced by IB1 resulted from an increased stability towards degradation. Modulation of the stability of specific JNK splice variants represents therefore a newly identified mechanism used by IB1 to regulate the JNK MAPK pathway.
Department of Physiology, Biology and Medicine Faculty, University of Lausanne, Bugnon 7, 1005 Lausanne, Switzerland.
Jiang-Yan
JY
Yang
Nathalie
N
Moulin
Miguel X
MX
van Bemmelen
Gilles
G
Dubuis
Thomas
T
Tawadros
Jacques-Antoine
JA
Haefliger
Gérard
G
Waeber
Christian
C
Widmann
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D004795:Enzyme Stability; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism; D051381:Rats
D048868:Adaptor Proteins, Signal Transducing; C110528:Mapk8ip1 protein, rat; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8