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MIXL1 (Mix1 homeobox-like 1 (Xenopus laevis))
Aaron Raymond, Lalitha Nagarajan
Departement of Genetics, Box 1010, MD Anderson cancer Center, 1515 Holcombe Blvd, Houston Tx 77030,
USA (AR, LN)
Published in Atlas Database: August 2010
Online updated version : http://AtlasGeneticsOncology.org/Genes/MIXL1ID47624ch1q42.html
DOI: 10.4267/2042/45016
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2011 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
DNA/RNA
Other names: MGC138179, MILD1, MIX, MIXL
HGNC (Hugo): MIXL1
Location: 1q42.12
Local order: MIXL1 is flanked on its 3' end by Lin9.
This proximity is evolutionarily conserved.
Description
MIXL1 is 2131 bps long and consists of two exons of
length 393 bp and 306 bp, and one intron (Guo et al.,
2002; Sahr et al., 2002).
Transcription
MIXL1 is transcribed to a full-length 699 bp mRNA.
There are no known splice variants.
Pseudogene
There are no known pseudogenes for MIXL1.
MIXL1 genomic context on 1q42.12.
Genomic organisation of MIXL1.
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(5)
419
MIXL1 (Mix1 homeobox-like 1 (Xenopus laevis))
Raymond A, Nagarajan L
Representation and comparison of Human MIXL1, Mouse Mixl1, Chicken Mixl1, and Xenopus Mix.1 protein domains. The Mix family of
proteins all contain evolutionarily conserved homeodomain and C-terminal acidic domains. Human, mouse and chicken also share a
conserved N-terminal proline rich domain. While these three domains are highly conserved, the remainder of protein varies significantly
between species.
Homology
Protein
MIXL1 is a member of the Mix/Bix family of
transcription factors, of which it is the only member
identified in humans. It is also a member of the larger
grouping of paired type homeoboxes, a family of genes
which share sequence similarity in the homeobox
domain with paired box family (PAX).
MIXL1 shares 41% sequence similarity to its chicken
homolog, and 69% to its mouse homolog. Its
homeodomain is highly conserved across species,
sharing identity of 66% to that of Xenopus Mix.1, 79%
to that of chicken Mixl1, and 94% to that of mouse
Mixl1.
Description
MIXL1 is a paired type homeobox protein which has
232 amino acids, and a molecular weight of 27 kDa.
The protein contains three identified domains: a
proline-rich domain, a paired-type homeobox, and a cterminal acidic domain. While MIXL1 does have an
expected weight of 27 kDa, it will migrate on a
Western Blot at 36 kDa (Guo et al., 2002). MIXL1 is
phosphorylated in the amino-terminal region at Tyr20
(Guo et al., 2006).
Expression
MIXL1 expression is restricted to embryonic
mesendoderm precursors and adult hematopoietic stem
cells and progenitors.
Implicated in
Localisation
Disease
MIXL1 is aberrantly expressed in patient samples
derived from Hodgkin's lymphoma, along with the
following Hodgkin cell lines: L-1236, L-428, HDMyZ, HD-LM2, MDA-E, MDA-V, KM-H2, and Daudi
(Drakos et al., 2007).
Hodgkin's lymphoma
MIXL1 expression is predominantly nuclear.
Function
MIXL1 is paired-type homeobox transcription factor,
and as such preferentially binds to the DNA sequence
TAAT. MIXL1 homologs preferentially bind as dimers
to 11 bp palindromic sequences consisting of two
TAAT segments and a three nucleotide spacer (Wilson
et al., 1993).
MIXL1 expression is required for both mesendoderm
development and hematopoiesis. The MIXL1 homologs
are necessary intermediate factors to the BMP4 (bone
morphogenetic protein 4)-mediated mesendoderm
formation, as dominant negative mutants block this
pathway (Mead et al., 1996). Development into
mesoderm and endoderm cell layers is dependant on
the expression collaborating factors.
MIXL1 expression is required for the early stages of
hematopoiesis and is normally expressed in all early
hematopoietic precursor types (Guo et al., 2002).
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(5)
T-cell NHL lymphoma
Disease
MIXL1 is aberrantly expressed in patient samples
derived from High Grade T-cell non-Hodgkin's
lymphoma, along with the following T-cell NHL
established lines: Karpas 299, MAC2A, SR-786, and
Peer (Drakos et al., 2007; Guo et al., 2002).
B-cell NHL lymphoma
Disease
MIXL1 is aberrantly expressed in patient samples
derived from High Grade B-cell non-Hodgkin's
lymphoma, along with the following B-cell NHL
established lines: SKI-DLBL, DB, DOHH1, IM-9,
420
MIXL1 (Mix1 homeobox-like 1 (Xenopus laevis))
Raymond A, Nagarajan L
Mino, Sp-53, Z-138, and CJ (Drakos et al., 2007; Guo
et al., 2002).
References
Acute myeloid leukemia
Wilson D, Sheng G, Lecuit T, Dostatni N, Desplan C.
Cooperative dimerization of paired class homeo domains on
DNA. Genes Dev. 1993 Nov;7(11):2120-34
Disease
Retroviral transduction of Mixl1 into mouse bone
marrow resulted in transplantable acute myeloid
leukemia in all lethally irradiated recipient mice after a
latency period (Glaser et al., 2006).
The following established AML cell lines aberrantly
express MIXL1: U937, KG1, and ML3 (Guo et al.,
2002).
Mead PE, Brivanlou IH, Kelley CM, Zon LI. BMP-4-responsive
regulation of dorsal-ventral patterning by the homeobox protein
Mix.1. Nature. 1996 Jul 25;382(6589):357-60
Guo W, Chan AP, Liang H, Wieder ED, Molldrem JJ, et al. A
human Mix-like homeobox gene MIXL shows functional
similarity to Xenopus Mix.1. Blood. 2002 Jul;100(1):89-95
Hwang HC, Martins CP, Bronkhorst Y, Randel E, Berns A,
Fero M, Clurman BE. Identification of oncogenes collaborating
with p27Kip1 loss by insertional mutagenesis and highthroughput insertion site analysis. Proc Natl Acad Sci U S A.
2002 Aug 20;99(17):11293-8
Chronic myeloid leukemia
Disease
MIXL1 is aberrantly expressed in the K562 established
cell line (Guo et al., 2002).
Sahr K, Dias DC, Sanchez R, Chen D, Chen SW, Gudas LJ,
Baron MH. Structure, upstream promoter region, and functional
domains of a mouse and human Mix paired-like homeobox
gene. Gene. 2002 May 29;291(1-2):135-47
T-cell leukemia
Disease
The Mixl1 promoter in mouse was identified as a site
of viral insertion, using the Moloney murine leukemia
virus, which collaborates with loss of p27 in induction
of lymphomagenesis (Hwang et al., 2002).
MIXL1 is aberrantly expressed in the following T-cell
leukemia established lines: Jurkat, SKW-3, and CEM
(Drakos et al., 2007; Guo et al., 2002).
Glaser S, Metcalf D, Wu L, Hart AH, DiRago L, et al. Enforced
expression of the homeobox gene Mixl1 impairs hematopoietic
differentiation and results in acute myeloid leukemia. Proc Natl
Acad Sci U S A. 2006 Oct 31;103(44):16460-5
Guo W, Nagarajan L. Amino terminal tyrosine phosphorylation
of human MIXL1. J Mol Signal. 2006 Dec 5;1:6
Drakos E, Rassidakis GZ, Leventaki V, Guo W, Medeiros LJ,
Nagarajan L. Differential expression of the human MIXL1 gene
product in non-Hodgkin and Hodgkin lymphomas. Hum Pathol.
2007 Mar;38(3):500-7
B-cell leukemia
Disease
MIXL1 is aberrantly expressed in the following B-cell
leukemia established lines: NALM6, REH-1 (Drakos et
al., 2007; Guo et al., 2002).
Atlas Genet Cytogenet Oncol Haematol. 2011; 15(5)
This article should be referenced as such:
Raymond A, Nagarajan L. MIXL1 (Mix1 homeobox-like 1
(Xenopus laevis)). Atlas Genet Cytogenet Oncol Haematol.
2011; 15(5):419-421.
421