All-trans retinoic acid induces p62DOK1 and p56DOK2 expression which enhances induced differentiation and G0 arrest of HL-60 leukemia cells
Copyright policy )All-trans retinoic acid induces p62DOK1 and p56DOK2 expression which enhances induced differentiation and G0 arrest of HL-60 leukemia cells
p62(DOK1) (DOK1) and p56(DOK2) (DOK2) are sequence homologs that act as docking proteins downstream of receptor or nonreceptor tyrosine kinases. Originally identified in chronic myelogenous leukemia cells as a highly phosphorylated substrate for the chimeric p210(bcr-abl) protein, DOK1 was suspected to play a role in leukemogenesis. However, p62(DOK1-/-) fibroblast knockout cells were found to have enhanced MAPK signaling and proliferation due to growth factors, suggesting negative regulatory capabilities for DOK1. The role of DOK1 and DOK2 in leukemogeneis thus is enigmatic. The data in this report show that both the DOK1 and the DOK2 adaptor proteins are constitutively expressed in the myelomonoblastic leukemia cell line, HL-60, and that expression of both proteins is induced by the chemotherapeutic differentiation causing agents, all-trans retinoic acid (atRA) and 1,25-dihydroxyvitamin D3 (VD3). Ectopic expression of either protein enhances atRA- or VD3-induced growth arrest, differentiation, and G(0)/G(1) cell cycle arrest and results in increased ERK1/2 phosphorylation. DOK1 and DOK2 are similarly effective in these capabilities. The data provide evidence that DOK1 and DOK2 proteins have a similar role in regulating cell proliferation and differentiation and are positive regulators of the MAPK signaling pathway in this context.
- Cornell University United States
Mitogen-Activated Protein Kinase Kinases, Gene Expression Regulation, Leukemic, MAP Kinase Signaling System, Gene Expression Profiling, Cell Cycle, Molecular Sequence Data, RNA-Binding Proteins, Cell Differentiation, HL-60 Cells, Flow Cytometry, Phosphoproteins, Leukemia, Myelomonocytic, Acute, DNA-Binding Proteins, Phenotype, Calcitriol, Cell Line, Tumor, Humans, Drug Screening Assays, Antitumor, Adaptor Proteins, Signal Transducing, Cell Proliferation
Mitogen-Activated Protein Kinase Kinases, Gene Expression Regulation, Leukemic, MAP Kinase Signaling System, Gene Expression Profiling, Cell Cycle, Molecular Sequence Data, RNA-Binding Proteins, Cell Differentiation, HL-60 Cells, Flow Cytometry, Phosphoproteins, Leukemia, Myelomonocytic, Acute, DNA-Binding Proteins, Phenotype, Calcitriol, Cell Line, Tumor, Humans, Drug Screening Assays, Antitumor, Adaptor Proteins, Signal Transducing, Cell Proliferation
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).17 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!