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A Chromatin Immunoprecipitation Screen Reveals Protein Kinase Cβ as a Direct RUNX1 Target Gene
Ist Teil von
The Journal of biological chemistry, 2004-01, Vol.279 (2), p.825
Ort / Verlag
American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
2004
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
RUNX1 (also known as AML1) is a DNA-binding transcription factor that functions as a tumor suppressor and developmental determinant
in hematopoietic cells. Target promoters have been identified primarily through the use of differential expression strategies
and candidate gene approaches but not biochemical screens. Using a chromatin immunoprecipitation screen, we identified protein
kinase Cβ as a direct RUNX1 target gene and demonstrate that endogenous RUNX1 binds the chromatinized protein kinase Cβ promoter
of U937 cells. A phylogenetically conserved RUNX1-binding site within the PKC β promoter binds RUNX1 in electrophoretic mobility shift analyses and confers RUNX1 responsiveness on a heterologous promoter.
Changes in RUNX1 activity affect endogenous protein kinase Cβ expression, and a dominant-negative form of RUNX1 protects U937
cells from apoptotic stimuli previously shown to be dependent on protein kinase Cβ. This protection can be reversed by the
ectopic expression of protein kinase Cβ. Together these findings demonstrate that protein kinase Cβ is a direct, downstream
target of RUNX1 and links RUNX1 to a myeloid apoptotic pathway.
Sprache
Englisch
Identifikatoren
ISSN: 0021-9258
eISSN: 1083-351X
DOI: 10.1074/jbc.M309524200
Titel-ID: cdi_highwire_biochem_279_2_825
Format
–
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