ArticleExperimental cell research2007
Expression of human kinase suppressor of Ras 2 (hKSR-2) gene in HL60 leukemia cells is directly upregulated by 1,25-dihydroxyvitamin D(3) and is required for optimal cell differentiation.
Article in Experimental cell research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- RAF Kinase Inhibitor Protein in Myeloid Leukemogenesis.International journal of molecular sciences · 2019Review
- Spatial regulation of ARAF controls the MST2-Hippo pathway.Small GTPases · 2019Article
- Differential localization of A-Raf regulates MST2-mediated apoptosis during epithelial differentiation.Cell death and differentiation · 2016Article
- Inhibitors for the Vitamin D Receptor-Coregulator Interaction.Vitamins and hormones · 2016Review
- The Potential of Vitamin D-Regulated Intracellular Signaling Pathways as Targets for Myeloid Leukemia Therapy.Journal of clinical medicine · 2015Review
- Gene expression profiles in human and mouse primary cells provide new insights into the differential actions of vitamin D3 metabolites.PloS one · 2013Article
- Dual role of hematopoietic progenitor kinase 1 (HPK1) as a positive regulator of 1α,25-dihydroxyvitamin D-induced differentiation and cell cycle arrest of AML cells and as a mediator of vitamin D resistance.Cell cycle (Georgetown, Tex.) · 2012Article
- MicroRNA-32 upregulation by 1,25-dihydroxyvitamin D3 in human myeloid leukemia cells leads to Bim targeting and inhibition of AraC-induced apoptosis.Cancer research · 2011Article
- Oncoprotein Cot1 represses kinase suppressors of Ras1/2 and 1,25-dihydroxyvitamin D3-induced differentiation of human acute myeloid leukemia cells.Journal of cellular physiology · 2011Article
- Inhibition of Cot1/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D(3).Cell cycle (Georgetown, Tex.) · 2010Article
- Expression of MAP3 kinase COT1 is up-regulated by 1,25-dihydroxyvitamin D3 in parallel with activated c-jun during differentiation of human myeloid leukemia cells.The Journal of steroid biochemistry and molecular biology · 2010Article
- 1,25-dihydroxyvitamin D3 enhances the apoptotic activity of MDM2 antagonist nutlin-3a in acute myeloid leukemia cells expressing wild-type p53.Molecular cancer therapeutics · 2010Article
- Vitamin D3-driven signals for myeloid cell differentiation--implications for differentiation therapy.Leukemia research · 2010Review
- hKSR-2, a vitamin D-regulated gene, inhibits apoptosis in arabinocytosine-treated HL60 leukemia cells.Molecular cancer therapeutics · 2008Article
- Induction of differentiation of human leukemia cells by combinations of COX inhibitors and 1,25-dihydroxyvitamin D3 involves Raf1 but not Erk 1/2 signaling.Cell cycle (Georgetown, Tex.) · 2008Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Induction of terminal differentiation of neoplastic cells offers potential for a novel approach to cancer therapy. One of the agents being investigated for this purpose in preclinical studies is 1,25-dihydroxyvitamin D(3) (1,25D), which can convert myeloid leukemia cells into normal monocyte-like cells, but the molecular mechanisms underlying this process are not fully understood. Here, we report that 1,25D upregulates the expression of hKSR-2, a new member of a small family of proteins that exhibit evolutionarily conserved function of potentiating ras signaling. The upregulation of hKSR-2 is direct, as it occurs in the presence of cycloheximide, and occurs primarily at the transcriptional level, via activation of vitamin D receptor, which acts as a ligand-activated transcription factor. Two VDRE-type motifs identified in the hKSR-2 gene bind VDR-RXR alpha heterodimers present in nuclear extracts of 1,25D-treated HL60 cells, and chromatin immunoprecipitation assays show that these VDRE motifs bind VDR in 1,25D-dependent manner in intact cells, coincident with the recruitment of RNA polymerase II to these motifs. Treatment of the cells with siRNA to hKSR-2 reduced the proportion of the most highly differentiated cells in 1,25D-treated cultures. These results demonstrate that hKSR-2 is a direct target of 1,25D in HL60 cells, and is required for optimal monocytic differentiation.
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