Phosphorylation of Serine 337 of NF-κB p50 Is Critical for DNA Binding*
By S. Hou, H. Guan, R. Ricciardi. Journal of Biological Chemistry, 2003
84 citations recorded by the source corpus.
It has been demonstrated that phosphorylation of the p50 subunit of NF-κB is required for efficient DNA binding, yet the specific phospho-residues of p50 have not been determined. In this study, we substituted all of the serine and conserved threonine residues in the p50 Rel homology domain and identified three serine residues, Ser65, Ser337, and Ser342, as critical for DNA binding without affecting dimerization. Although substitution with negatively charged aspartic acid at each of these positions failed to restore DNA binding, substitution with threonine, a potential phospho-acceptor, retained DNA binding for residues 65 and 337. In particular, Ser337, in a consensus site for protein kinase A (PKA) and other kinases, was shown to be phosphorylated both in vitro and in vivo. Importantly, phosphorylation of Ser337 by PKA in vitro dramatically increased DNA binding of p50. This study shows for the first time that the DNA binding ability of NF-κB p50 subunit is regulated through phosphorylation of residue Ser337, which has implications for both positive and negative control of NF-κB transcription.
Subfields: Cancer Research, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/32fddadf988486fe7da0bf1121503b27023eae3e
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
In Molecular Biology
In Oncology
Citations in the corpus
- The Regulation of NF-κB Subunits by Phosphorylation (2016, background): “S337 lies in a Protein kinase A (PKA) consensus site and PKA has been demonstrated to phosphorylate p50 at S337 in vitro and in vivo [23,24].”
- Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway (2006, background): “Similarly, as discussed above, p50 is phosphorylated at the RelA Ser-276 equivalent, that is, Ser-337 (Hou et al., 2003; Guan et al., 2005).”