Adapter protein NRBP associates with Jab1 and negatively regulates AP-1 activity.
Jun activation domain-binding protein 1 (Jab1) is a coactivator of activating protein-1 (AP-1) and is the fifth component of the COP9 signalosome complex. It interacts with a variety of proteins and plays important roles in diverse signaling pathways and cellular function including oncogenesis. We show here that Jab1 interacts in vivo with nuclear receptor binding protein (NRBP), an evolutionarily conserved adapter protein with a kinase-like domain. We further show that NRBP inhibits Jab1-induced phosphorylation of c-Jun and AP-1 activation. Finally, overexpression of NRBP in mammalian cells specifically inhibits AP-1 activation by various stimuli. Taken together, our data suggest that NRBP may be an important negative regulator of Jab1-mediated functions such as gene transcription and tumor progression.
Wang
Hui
H
Department of Life Science and Biotechnology, Shanghai Jiaotong University, 1954 Huashan Road, Shanghai 200030, China.
Sun
Xiaoqing
X
Luo
Ying
Y
Lin
Zhixin
Z
Wu
Jun
J
D001665:Binding Sites; D000075686:COP9 Signalosome Complex; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins
D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C410809:NRBP1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D033921:Vesicular Transport Proteins; D011494:Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex