title: High mobility group box-1 protein acts as a coactivator of nuclear factor of activated T cells-2 in promoting interleukin-2 transcription.
abstract: High mobility group box-1 protein, an abundant and conserved constituent of vertebrate nuclei, has recently been reported to be an endogenous immune signal [Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, et al. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Reports 2004;5:825-30]. High mobility group box-1 protein can trigger the release of interleukin-2 and interleukin-12 from lymphocytes. However, at present the underlying mechanism remains unknown. It has been clarified that nuclear factor of activated T cells-2 transduces most immunological signals in T cells and modulates the production of interleukin-2. So it is natural that we asked whether high mobility group box-1 protein could promote production of interleukin-2 in a nuclear factor of activated T cells-2-dependent way. Our experiments firstly showed that high mobility group box-1 protein could bind to nuclear factor of activated T cells-2 in vivo and in vitro. High mobility group box-1 protein cotransfection markedly upregulated the transcription activity of nuclear factor of activated T cells-2 in promoting interleukin-2 reporter gene transcription, which was demonstrated to be dose-dependent. Cotransfection of high mobility group box-1 protein and nuclear factor of activated T cells-2 induced an 18.4-time increase of interleukin-2 activity in 293T cells and a 117.7-time increase in Hela cells. Moreover, inhibition of either high mobility group box-1 protein or nuclear factor of activated T cells -2 expression by sRNAi led to significant decrease of transcription activity of interleukin-2 reporter gene, suggesting that high mobility group box-1 protein and nuclear factor of activated T cells-2 both take important roles in facilitating interleukin-2 transcription, and high mobility group box-1 protein could act as a coactivator for nuclear factor of activated T cells-2 in enhancing transcription of interleukin-2. This discovery has not been reported elsewhere, and helps to understand the newly highlighted immunological role of high mobility group box-1 protein.
authors.affiliation: Surgical Intensive Care Unit, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Yong-ming
authors.initials: YM
authors.lastname: Yao
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Ding
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Yuan
authors.forename: Qing
authors.initials: Q
authors.lastname: Song
authors.forename: Qi-nong
authors.initials: QN
authors.lastname: Ye
authors.forename: Cui-fen
authors.initials: CF
authors.lastname: Huang
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D020218:Response Elements / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D024243:HMGB1 Protein; D007155:Immunologic Factors; D007376:Interleukin-2; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D034741:RNA, Small Interfering