Elucidation of phosphorylation mechanism participate in nucreocytoplasmic shuttling and secretion of HMGB1

2015 Fiscal Year Final Research Report

• Project/Area Number: 25870990
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry; Functional biochemistry
• Research Institution: Kyushu Institute of Technology (2014-2015); Kurume University (2013)
• Principal Investigator: Taira Junichi 九州工業大学, 大学院情報工学研究院, 助教 (20549612)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: HMGB1 / PP2A / 核移行シグナル / PKC / GSK-3 / CK2

Outline of Final Research Achievements

Phosphorylation of high mobility group box 1 (HMGB1) is involved in the subcellular translocation of the protein and subsequent secretion. Phosphorylation of serine residues in the two nuclear localization signals (NLS1 and NLS2) promotes nucleocytoplasmic relocation of HMGB1. In this study, it was suggested that protein phosphatase 2A (PP2A) correlates in the nucleocytoplasmic shuttling of HMGB1 through dephosphorylation of specific phosphoserines within NLS1. Next, kinases that phosphorylate serine residues within NLS1 were predicted, and an in vitro kinase assay was performed. Among the predicted kinases, protein kinase C phosphorylated Ser46 of HMGB1-derived peptides, and a mutagenesis experiment implied that the phosphorylation could induce translocation of HMGB1 to the cytosol.

Free Research Field

生化学