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J. Biol. Chem., Vol. 275, Issue 37, 28507-28512, September 15, 2000
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§,
§¶,
,
,
**,
,
, and
§§
From the The CD11a/CD18 leukocyte integrin (LFA-1; also
known as
Centro de Investigaciones Biológicas,
Consejo Superior de Investigaciones Científicas,
Madrid 28006, Spain and the

Departamento de Inmunología,
Facultad de Medicina, Universidad de Córdoba,
Córdoba, 14071 Spain
L/
2) mediates leukocyte transendothelial
migration during immune and inflammatory responses and participates in
lymphoma metastasis. CD11a/CD18 leukocyte-restricted expression is
controlled by the CD11a gene promoter, which confers
tissue-specific expression to reporter genes in vitro and
in vivo. DNase I protection analysis of the CD11a
proximal gene promoter revealed DNA-protein interactions centered
at position -110 (CD11a-110). Disruption of CD11a-110 reduced
CD11a promoter activity in a cell type-specific manner, as
it reduced its activity by 70% in Jurkat lymphoid cells, whereas the
effect was considerably lower in K562 and HepG2 cells. Electrophoretic mobility shift assays showed evidence of cell type-specific
differences in CD11a-110 binding and indicated its specific recognition
by members of the polyomavirus enhancer-binding protein 2/core binding factor (CBF)/acute myeloid leukemia (AML) family of transcription factors. AML1B/CBF
transactivated the CD11a promoter,
with AML1B/CBF
-mediated transactivation being completely dependent
on the integrity of the CD11a-110 element. Therefore, CBF/AML factors
play a role in the cell type-restricted transcription of the
CD11a integrin gene through recognition of CD11a-110. The
involvement of CBF/AML factors in CD11a expression raises the
possibility that CD11a/CD18 expression might be deregulated in acute
myeloid and B-lineage acute lymphoblastic leukemias, thus contributing
to their altered adhesion and metastatic potential.
Recipients of predoctoral and postdoctoral fellowships from
Comunidad Autónoma de Madrid.
**
Current address: Centro de Investigacion, Almirall Prodesfarma,
S.A., Cardener 68-74, Barcelona 08024, Spain.
§§
To whom correspondence should be addressed. Tel.: 34-91-5644562, ext. 4312; Fax: 34-91-5627518; E-mail: acorbi@cib.csic.es.
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