The RAC specific guanine nucleotide exchange factor Asef functions downstream from TEL-AML1 to promote leukaemic transformation.
TEL-AML1 is an oncogenic fusion protein associated with childhood pre-B acute lymphoblastic leukaemia. From published microarray datasets we identified the Rho Guanine Nucleotide Exchange Factor (RhoGEF) Asef to be associated with TEL-AML1 leukaemia. However, the Asef gene is not a direct target of TEL-AML1 transcriptional control. Forced expression of Asef in vitro induced and maintained proliferation of haemaopoietic progenitor cells and co-operated with TEL-AML1 greatly to enhance proliferation and haemopoietic colony size. In haemopoietic transplantation reconstitution assays Asef and TEL-AML1 together failed to induce a leukaemic phenotype.
Lyons
Ruth
R
Unit of Molecular Haematology and Cancer Biology, University College London Institute of Child Health, London, United Kingdom.
Williams
Owen
O
Morrow
Michelle
M
Sebire
Neil
N
Hubank
Mike
M
Anderson
John
J
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D050676:Core Binding Factor Alpha 2 Subunit / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D064067:Rho Guanine Nucleotide Exchange Factors; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D020662:Guanine Nucleotide Exchange Factors; D015514:Oncogene Proteins, Fusion; D064067:Rho Guanine Nucleotide Exchange Factors; C576602:ARHGEF4 protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein