Trib1 is an important adaptor that connects the MAP kinase pathway with C/EBPa in leukemogenesis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430121
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Yokoyama Takashi 公益財団法人がん研究会, 発がん研究部, 研究員 (00535833)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Trib1 / C/EBPα / Hoxa9 / Bcl11a / 白血病 / ノックアウトマウス / ChIPシークエンス

Outline of Final Research Achievements

Trib1 is a collaborator of Hoxa9/Meis1 in AML and it by itself induces AML through enhancement of MAP kinase signaling and degradation of C/EBPa. Biological phenotypes of Hoxa9-immortalized cells with different Trib1 expression status, Trib1 hi, Trib1 lo and Trib1 null, were compared. Proliferation, DNA synthesis and pERK was increased in the Trib1 hi cell. Genome-wide DNA-binding region of Hoxa9 and C/EBPa were then assessed in Trib1 hi, Trib1 lo and Trib1 null and potentially important Hoxa9 and C/EBPa target genes were searched in nearest neighbor genes of their binding peaks of which expression was 1.5-fold up- or down-regulated by Trib1 overexpression. Cdk6, Kit, Cd44, and Cd34 are such Hoxa9 target candidates up-regulated by Trib1. Also, Idh1, Tet2 and Vcam1 are down-regulated genes. These results suggested that Trib1 might alter cell cycle progression and differentiation by modulating Hoxa9-mediated transcriptional program and by repressing C/EBPa target tumor suppressor genes.

Free Research Field

医薬理学