A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus Mix.1.
Molecular events involved in specification of early hematopoietic system are not well known. In Xenopus, a paired-box homeodomain family (Mix.1-4) has been implicated in this process. Although Mix-like homeobox genes have been isolated from chicken (CMIX) and mice (Mml/MIXL1), isolation of a human Mix-like gene has remained elusive. We have recently isolated and characterized a novel human Mix-like homeobox gene with a predicted open reading frame of 232 amino acids designated the Mix.1 homeobox (Xenopus laevis)-like gene (MIXL). The overall identity of this novel protein to CMIX and Mml/MIXL1 is 41% and 69%, respectively. However, the identity in the homeodomain is 66% to that of Xenopus Mix.1, 79% to that of CMIX, and 94% to that of Mml/MIXL1. In normal hematopoiesis, MIXL expression appears to be restricted to immature B- and T-lymphoid cells. Several acute leukemic cell lines of B, T, and myeloid lineage express MIXL suggesting a survival/block in differentiation advantage. Furthermore, Xenopus animal cap assay revealed that MIXL could induce expression of the alpha-globin gene, suggesting a functional conservation of the homeodomain. Isolation of the MIXL gene is the first step toward understanding novel regulatory circuits in early hematopoietic differentiation and malignant transformation.
Guo
Wei
W
Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.
Chan
Agnes Pui-Yee
AP
Liang
Hong
H
Wieder
Eric D
ED
Molldrem
Jeffrey J
JJ
Etkin
Laurence D
LD
Nagarajan
Lalitha
L
D000818:Animals; D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D005801:Genes, Homeobox / Q000235:genetics* / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins
C115868:Bix1 protein, Xenopus; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D017874:Immediate-Early Proteins; C100368:Mix1 protein, Xenopus; D029867:Xenopus Proteins