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Adapter protein NRBP associates with Jab1 and negatively regulates AP-1 activity
Hui Wang1, Xiaoqing Sun, Ying Luo
1Department of Life Science and Biotechnology, Shanghai Jiaotong University, 1954 Huashan Road, Shanghai 200030, China.
Abstract:
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.
Insights
Nuclear receptor binding protein (NRBP) inhibits Jun activation domain-binding protein 1 (Jab1) activity. This suggests NRBP acts as a negative regulator in gene transcription and tumor progression.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Oncogenesis
Background:
- Jun activation domain-binding protein 1 (Jab1) is a coactivator of activating protein-1 (AP-1) and a component of the COP9 signalosome complex.
- Jab1 plays critical roles in cell signaling, cellular functions, and oncogenesis through interactions with various proteins.
Purpose of the Study:
- To investigate the interaction between Jab1 and nuclear receptor binding protein (NRBP).
- To determine the functional consequence of NRBP on Jab1-mediated AP-1 activation.
- To explore the potential role of NRBP as a regulator of Jab1 functions.
Main Methods:
- In vivo interaction studies between Jab1 and NRBP.
- Analysis of Jab1-induced c-Jun phosphorylation and AP-1 activation.
- Overexpression studies of NRBP in mammalian cells to assess AP-1 activation.
Main Results:
- Jab1 interacts in vivo with nuclear receptor binding protein (NRBP).
- NRBP inhibits Jab1-induced phosphorylation of c-Jun and subsequent AP-1 activation.
- Overexpression of NRBP specifically suppresses AP-1 activation stimulated by various factors in mammalian cells.
Conclusions:
- NRBP interacts with Jab1 and negatively regulates its functions.
- NRBP may serve as a crucial negative regulator of Jab1-mediated gene transcription and tumor progression.
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