PKA對RNF4的磷酸化可促進含有CCAAT-box基因的轉錄表現
Phosphorylation of RNF4 by protein kinase A contributes to CCAAT-box related transcription
Date Issued
2006
Date
2006
Author(s)
Chang, Feng-Chuan
DOI
en-US
Abstract
The small nuclear RING finger protein 4 (RNF4) is a recently identified human RING finger protein that contains C3HC4-type zinc finger motif in the C-terminal region. RNF4 has been implicated in transcriptional regulation through interacting with a variety of nuclear proteins, and functions as a transcriptional corepressor or coactivator.
According to our previous study, we found that coactivator RNF4 is involved in the GTP cyclohydrolase I (GCH) gene expression and we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT-box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 is a coactivator of the CCAAT box binding protein nuclear factor Y (NF-Y). Overall, we prove that RNF4 imposes functional importance on GCH promoter.
In this study, I demonstrated that protein kinase A (PKA)-dependent phosphorylation of RNF4 activates the CCAAT-box containing GCH promoter. Results from biological and functional characterizations of RNF4 mutants defective in PKA phosphorylation sites suggest that PKA-dependent RNF4 phosphorylation is important for its role in GCH promoter activation. S127 and S166 of RNF4 are important phosphorylation sites in RNF4-mediated CAAT-box activation by PKA. Furthermore, I also found that the C-terminal basic region is essential for RNF4 phosphorylation and activation by PKA.
In summary, we first illustrate a novel RNF4-mediated PKA signaling pathway that leads to the activation of GCH promoter.
Subjects
協同抑制因子
活化因子
磷酸化
RNF4
PKA
phosphorylation
Type
other
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