title: The effect of PKC phosphorylation on the "architectural" properties of HMGB1 protein.
abstract: High mobility group box (HMGB)1 protein acts as an architectural element, promoting the assembly of active nucleoprotein complexes due to its ability to bend DNA and to bind preferentially to distorted DNA structures. The behavior of HMGB1 as an "architect" of chromatin defines it as an important factor in many cellular processes such as repair, replication and remodeling. It was shown that the post-synthetic acetylation of HMGB1 at Lys2 modulated its essential properties as a structure-specific nuclear protein. We studied the role of PKC phosphorylation on the "architectural" properties of HMGB1, (i) the effect for the formation of a stable complex with DNA damaged by the anti-tumour drug cis-platinum and (ii) the influence on the ability of HMGB1 protein to bend short DNA fragments. PKC-phosphorylated recombinant HMGB1 increased about an order of magnitude its affinity to cis-platinated DNA, a finding that has already been reported for in vivo acetylated protein. Regarding the effect on the protein's DNA bending ability, it was enhanced upon phosphorylation as demonstrated by the stimulation of DNA circularization. We showed also that PKC phosphorylated the recombinant protein in vitro simultaneously at two target sites. Our results demonstrate that the PKC phosphorylation of HMGB1 has a considerable effect on the fundamental properties of the protein; therefore this post-synthetic modification may serve as a modulator of the HMGB1 participation in different nuclear processes.
authors: Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors: Iva
authors: I
authors: Ugrinova
authors: Stanislava
authors: S
authors: Zlateva
authors: Evdokia
authors: E
authors: Pasheva
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats
chemical_list: D024243:HMGB1 Protein; D004247:DNA; D011493:Protein Kinase C; D008239:Lysine