title: The role of Trib1 in myeloid leukaemogenesis and differentiation.
abstract: Tribbles homolog 1 (Trib1) was identified as a common integration site of the Homeobox a9 (Hoxa9)/murine ecotropic virus integration site 1 (Meis1) retrovirus in acute myeloid leukaemia (AML). Trib1 is by itself a transforming gene for myeloid cells but also significantly accelerates progression of Hoxa9/Meis1-induced AML. The strong transforming activity of Trib1 depends on its bi-directional function in CCAAT/enhancer-binding protein (C/EBPα) degradation and MAPK/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) activation. TRIB1 is also involved in a certain type of human AML and a TRIB1 somatic point mutation R107L was identified in a case of Down syndrome (DS)-related acute megakaryocytic leukaemia. Although Trib1 knockout (KO) did not suppress haematopoiesis in mouse bone marrow significantly, increase in mature granulocytes was observed and promotion of myeloid differentiation was associated with the increased C/EBPα protein. Trib1 thus plays an important role in myeloid cell development and transformation.
authors.affiliation: Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan takuro-ind@umin.net.
authors.forename: Takuro
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000208:Acute Disease; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008957:Models, Genetic; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D047908:Intracellular Signaling Peptides and Proteins; C493170:TRIB1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: CCAAT/enhancer binding protein (C/EBP); acute myeloid leukaemia (AML); haematopoiesis; mitogen-activated protein kinase (MAPK); tribbles homolog 1 (Trib1)