1. Analysis of the carcinogenic mechanism using mutagenesis
  2. Functional analysis of homeodomain proteins
  3. Functional analysis of chimeric genes in development of mesenchymal tumor and leukemia

Functional analysis of homeodomain proteins

Homeodomain proteins play an important role in maintenance and differentiation of the hematopoietic system. We found that Hoxa9/a9 and Meis1 are cooperatively activated in BXH2 mouse acute myeloid leukemia (AML). Moreover, AML is efficiently induced by co-introduction of Hoxa9 and Meis1 into mouse bone marrow cells. It is known that Meis1 is essential in normal hematopoiesis, and its exact role in hematopoiesis and leukemogenesis will be investigated by using the Meis1 conditional knock-out mouce. It is important to clarify how the DNA-binding Hox/Pbx/Meis complexes are regulated in leukemogenesis and hematopoiesis.

We have identified Trib1 as a specific collaborator for the Hoxa9/Meis1 pathway. As Trib family proteins are considered as modulators in the RAS/MAPK signaling and C/EBP transcription factors, it is important to know the functional significance of Hox/Meis and Trib1 cooperation.

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