title: Glucocorticoid-mediated co-regulation of RCAN1-1, E4BP4 and BIM in human leukemia cells susceptible to apoptosis.
abstract: Glucocorticoids (GCs) are known to induce apoptosis of leukemia cells via gene regulatory changes affecting key pro-and anti-apoptotic genes. Three genes previously implicated in GC-evoked apoptosis in the CEM human T-cell leukemia model, RCAN1, E4BP4 and BIM, were studied in a panel of human lymphoid and myeloid leukemia cell lines. Of the two RCAN1 transcripts, the synthetic GC Dexamethasone (Dex) selectively upregulates RCAN1-1, but not RCAN1-4, in GC-susceptible Sup-B15, RS4;11, Kasumi-1 cells but not in GC-resistant Sup T1 and Loucy cells. E4BP4 and BIM regulation correlated with that of RCAN1-1. A putative GRE and four EBPREs were identified within 1500bp upstream from the transcription start site of RCAN1-1. GC-refractory CEM C1-15 cells sensitized to GC-evoked apoptosis by ectopic E4BP4 expression, CEM C1-15mE#3, showed restored RCAN1-1 upregulation, suggesting that RCAN1-1 is a downstream target of E4BP4. A model for coordinated regulation of RCAN1-1, E4BP4 and BIM, and their role in GC-evoked apoptosis is proposed.
authors.affiliation: Department of Biology, California State University Northridge, Northridge, CA 91330-8303, USA. Electronic address: Gustavo.J.Saenz@kp.org.
authors.forename: G Jonatan
authors.initials: GJ
authors.lastname: Saenz
authors.affiliation: Department of Biology, California State University Northridge, Northridge, CA 91330-8303, USA. Electronic address: rebeka888@gmail.com.
authors.forename: Rebeka
authors.initials: R
authors.lastname: Hovanessian
authors.affiliation: Department of Biology, California State University Northridge, Northridge, CA 91330-8303, USA. Electronic address: andrew.d.gisis@my.csun.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gisis
authors.affiliation: Department of Biology, California State University Northridge, Northridge, CA 91330-8303, USA. Electronic address: rheem.medh@csun.edu.
authors.forename: Rheem D
authors.initials: RD
authors.lastname: Medh
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D000072224:Bcl-2-Like Protein 11; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C497440:NFIL3 protein, human; D011518:Proto-Oncogene Proteins; C108612:RCAN1 protein, human; D011965:Receptors, Glucocorticoid
keywords: Apoptosis; BIM; E4BP4; Glucocorticoids; Leukemia; RCAN1