The proposed studies investigate the mechanism by which retinoic acid regulates cell proliferation and differentiation. The studies will use th HL-60 human myeloblastic cell line which is an uncommitted hematopoietic precursor cell that can be induced to undergo myeloid or monocytic differentiation and GO growth arrest. The proposed experiments will determine: 1) the identity of a small ensemble of early differentiation and growth regulatory genes whose expression is induced by retinoic acid, 2) whether the induced expression of each specific gene depends on signalling through RARs, RXRs, which are ligand activated transcription factors, or ERK2 activated transcription factors, 3) which genes are essential for retinoic acid to induc either differentiation, RB tumor suppressor hypophosphorylation, or GO growth arrest, 4) which genes might act as central regulators seminal to inducing either differentiation, RB hypophosphorylation, or GO arrest.
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