A novel c-Jun N-terminal kinase (JNK)-binding protein WDR62 is recruited to stress granules and mediates a nonclassical JNK activation.
The c-Jun N-terminal kinase (JNK) is part of a mitogen-activated protein kinase (MAPK) signaling cascade. Scaffold proteins simultaneously associate with various components of the MAPK signaling pathway and play a role in signal transmission and regulation. Here we describe the identification of a novel scaffold JNK-binding protein, WDR62, with no sequence homology to any of the known scaffold proteins. WDR62 is a ubiquitously expressed heat-sensitive 175-kDa protein that specifically associates with JNK but not with ERK and p38. Association between WDR62 and JNKs occurs in the absence and after either transient or persistent stimuli. WDR62 potentiates JNK kinase activity; however it inhibits AP-1 transcription through recruitment of JNK to a nonnuclear compartment. HEK-293T cells transfected with WDR62 display cytoplasmic granular localization. Overexpression of stress granule (SG) resident proteins results in the recruitment of endogenous WDR62 and activated JNK to SG. In addition, cell treatment with arsenite results in recruitment of WDR62 to SG and activated JNK to processing bodies (PB). JNK inhibition results in reduced number and size of SG and reduced size of PB. Collectively, we propose that JNK and WDR62 may regulate the dynamic interplay between polysomes SG and PB, thereby mediating mRNA fate after stress.
Wasserman
Tanya
T
Department of Molecular Genetics, The Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa, Israel.
Katsenelson
Ksenya
K
Daniliuc
Sharon
S
Hasin
Tal
T
Choder
Mordechay
M
Aronheim
Ami
A
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000201:enzymology*; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D011506:Proteins; D018808:Transcription Factor AP-1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D048031:JNK Mitogen-Activated Protein Kinases