ArticleMolecular and cellular biology2004
Protein kinase C-mediated phosphorylation of the leukemia-associated HOXA9 protein impairs its DNA binding ability and induces myeloid differentiation.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 45 citations in OpenAlex.
- HOXA9 Regulome and Pharmacological Interventions in Leukemia.Advances in experimental medicine and biology · 2024Review
- Article
- Homeobox A4 suppresses vascular remodeling by repressing YAP/TEAD transcriptional activity.EMBO reports · 2020Article
- Direct and Indirect Targeting of HOXA9 Transcription Factor in Acute Myeloid Leukemia.Cancers · 2019Review
- Kinase Regulation of HOX Transcription Factors.Cancers · 2019Review
- Heterocyclic Diamidine DNA Ligands as HOXA9 Transcription Factor Inhibitors: Design, Molecular Evaluation, and Cellular Consequences in a HOXA9-Dependant Leukemia Cell Model.Journal of medicinal chemistry · 2019Article
- Mechanisms of Specificity for Hox Factor Activity.Journal of developmental biology · 2016Article
- Review
- The Role of Protein Arginine Methyltransferases in Inflammatory Responses.Mediators of inflammation · 2016Review
- Article
- HOXA9 methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules.Molecular and cellular biology · 2012Article
- Phosphorylation of HOX11/TLX1 on Threonine-247 during mitosis modulates expression of cyclin B1.Molecular cancer · 2010Article
- Polycomb repressor complex 2 regulates HOXA9 and HOXA10, activating ID2 in NK/T-cell lines.Molecular cancer · 2010Article
- MicroRNA-126 regulates HOXA9 by binding to the homeobox.Molecular and cellular biology · 2008Article
- Review
- HOXA9 participates in the transcriptional activation of E-selectin in endothelial cells.Molecular and cellular biology · 2007Article
- Delayed biosynthesis of varicella-zoster virus glycoprotein C: upregulation by hexamethylene bisacetamide and retinoic acid treatment of infected cells.Journal of virology · 2006Article
- TGFbeta/BMP inhibits the bone marrow transformation capability of Hoxa9 by repressing its DNA-binding ability.The EMBO journal · 2006Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
HOXA9 expression is a common feature of acute myeloid leukemia, and high-level expression is correlated with poor prognosis. Moreover, HOXA9 overexpression immortalizes murine marrow progenitors that are arrested at a promyelocytic stage of differentiation when cultured and causes leukemia in recipient mice following transplantation of HOXA9 expressing bone marrow. The molecular mechanisms underlying the physiologic functions and transforming properties of HOXA9 are poorly understood. This study demonstrates that HOXA9 is phosphorylated by protein kinase C (PKC) and casein kinase II and that PKC mediates phosphorylation of purified HOXA9 on S204 as well as on T205, within a highly conserved consensus sequence, in the N-terminal region of the homeodomain. S204 in the endogenous HOXA9 protein was phosphorylated in PLB985 myeloid cells, as well as in HOXA9-immortalized murine marrow cells. This phosphorylation was enhanced by phorbol ester, a known inducer of PKC, and was inhibited by a specific PKC inhibitor. PKC-mediated phosphorylation of S204 decreased HOXA9 DNA binding affinity in vitro and the ability of the endogenous HOXA9 to form cooperative DNA binding complexes with PBX. PKC inhibition significantly reduced the phorbol-ester induced differentiation of the PLB985 hematopoietic cell line as well as HOXA9-immortalized murine bone marrow cells. These data suggest that phorbol ester-induced myeloid differentiation is in part due to PKC-mediated phosphorylation of HOXA9, which decreases the DNA binding of the homeoprotein.
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