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LAF-4 encodes a lymphoid nuclear protein with transactivation potential
that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias
C Ma and LM Staudt
Metabolism Branch, National Cancer Institute, National Institutes of
Health, Bethesda, MD 20892, USA.
A novel human gene, LAF-4, was isolated from a subtracted cDNA library that
showed strong sequence similarity to AF-4, a gene that is translocated in
t(4;11)(q21;q23) acute lymphoblastic leukemias (ALLs). In t(4;11) ALL, the
AF-4 gene at 4q21 is translocated into the MLL locus at 11q23, resulting in
the expression of an MLL/AF-4 fusion protein that is the presumptive
oncoprotein. AF-4 and LAF-4 are homologous throughout their coding regions,
yet neither protein is related to previously cloned genes. Human LAF-4
readily hybridized with genes in mouse and chicken, thus showing that this
gene family has been highly conserved during vertebrate evolution. In mouse
tissues, LAF-4 mRNA was found to be present at highest levels in lymphoid
tissues, present at lower levels in brain and lung, and absent from other
tissues. In human and mouse lymphoid cell lines, LAF-4 expression was
highest in pre-B cells, intermediate in mature B cells, and absent in
plasma cells, thus pointing to a potential regulatory role for LAF-4 in
lymphoid development. Antibodies to LAF-4 showed it to be a nuclear protein
that showed an uneven, granular immunofluorescence pattern. In
vitro-translated LAF-4 was able to bind strongly to double-stranded DNA
cellulose. Furthermore, both LAF-4 and AF-4 had domains that activated
transcription strongly when fused to the GAL4 DNA-binding domain.
Interestingly, the AF-4 transactivation domain is retained in the MLL/AF-4
fusion protein; thus, it may contribute to the transforming potential of
the oncoprotein. Therefore, the cloning of LAF-4 has defined a new family
of potential regulatory proteins that may function in lymphoid development
and oncogenesis.
Volume 87,
Issue 2,
pp. 734-745,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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