title: Down-regulation of wild-type p53 activity interferes with apoptosis of IL-3-dependent hematopoietic cells following IL-3 withdrawal.
abstract: Overexpression of wild-type p53 in p53-deficient leukemic cells induces apoptosis, which can be inhibited by hematopoietic survival factors. This suggests that p53 may contribute to survival factor dependence. To assess the role of wild-type p53 in mediating apoptosis following survival factor withdrawal, we interfered with endogenous p53 activity in interleukin-3 (IL-3)-dependent cells. Extended survival without IL-3 was conferred by recombinant retroviruses encoding either a full-length p53 mutant or a C-terminal p53 miniprotein, both of which can act as negative-dominant inhibitors of wild-type p53. On the other hand, excess wild-type p53 activity failed to elicit apoptosis as long as IL-3 was present. We propose that p53 is a positive, though not exclusive, mediator of survival factor dependence in hematopoietic cells.
authors.affiliation: Department of Chemical Immunology, Science, Rehovot.
authors.forename: E
authors.initials: E
authors.lastname: Gottlieb
authors.forename: R
authors.initials: R
authors.lastname: Haffner
authors.forename: T
authors.initials: T
authors.lastname: von Rüden
authors.forename: E F
authors.initials: EF
authors.lastname: Wagner
authors.forename: M
authors.initials: M
authors.lastname: Oren
mesh_terms: D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D015536:Down-Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007377:Interleukin-3 / Q000502:physiology*; D051379:Mice; D009154:Mutation; D013696:Temperature; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: D007377:Interleukin-3; D016159:Tumor Suppressor Protein p53