Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein.
We show that homothorax (hth) is required for the Hox genes to pattern the body of the fruit fly, Drosophila melanogaster. hth is necessary for the nuclear localization of an essential HOX cofactor, Extradenticle (EXD), and encodes a homeodomain protein that shares extensive identity with the product of Meis1, a murine proto-oncogene. MEIS1 is able to rescue hth mutant phenotypes and can induce the cytoplasmic-to-nuclear translocation of EXD in cell culture and Drosophila embryos. Thus, Meis1 is a murine homolog of hth. MEIS1/HTH also specifically binds to EXD with high affinity in vitro. These data suggest a novel and evolutionarily conserved mechanism for regulating HOX activity in which a direct protein-protein interaction between EXD and HTH results in EXD's nuclear translocation.
Rieckhof
G E
GE
Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Casares
F
F
Ryoo
H D
HD
Abu-Shaar
M
M
Mann
R S
RS
D000825:Animal Structures / Q000502:physiology; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007951:Leukemia, Myeloid; D051379:Mice; D008969:Molecular Sequence Data; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors; C083405:exd protein, Drosophila; C108704:hth protein, Drosophila