HMGB1 protein inhibits DNA replication in vitro: a role of the acetylation and the acidic tail.
The high mobility group box (HMGB) 1 protein is a very abundant and conserved protein that is implicated in many key cellular events but its functions within the nucleus remain elusive. The role of this protein in replication of closed circular DNA containing a eukaryotic origin of replication has been studied in vitro by using native and recombinant HMGB1 as well as various modified HMGB1 preparations such as truncated protein, lacking its C-terminal tail, in vivo acetylated protein, and recombinant HMGB1 phosphorylated in vitro by protein kinase C (PKC). Native HMGB1 extracted from tumour cells inhibits replication and this effect is reduced upon acetylation and completely abolished upon removal of the acidic C-terminal tail. Recombinant HMGB1, however, fails to inhibit replication but it acquires such a property following in vitro phosphorylation by PKC.
Topalova
Dessislava
D
Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Ugrinova
Iva
I
Pashev
Iliya G
IG
Pasheva
Evdokia A
EA
D000107:Acetylation; D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects*; D004270:DNA, Circular / Q000378:metabolism; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012097:Repressor Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004270:DNA, Circular; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D006609:High Mobility Group Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D016590:Aphidicolin; D011493:Protein Kinase C