The gene encoding the granulocyte colony-stimulating factor receptor is a target for deregulation in pre-B ALL by the t(1;19)-specific oncoprotein E2A-Pbx1

Wb, de Lau; Hurenkamp, Jolanda; Berendes, P; Touw, I.P.; Hc, Clevers; Dijk, van Erik

doi:10.1038/sj.onc.1201967

Cited by 19 publications

(5 citation statements)

References 24 publications

(36 reference statements)

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“…In response to ligand-binding, surface expression of the mutant G-CSFR forms was found to be increased, which correlated with sustained intracellular activation and enhanced growth and survival responses to G-CSF [10,29,30,36]. Increased expression of the G-CSFR either at the mRNA or protein level has also been reported in patients with AML without antecedent SCN, and in patients with CML and acute and chronic lymphoid leukemias [37][38][39][40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Role of the proteasome in modulating native G-CSFR expression

Kindwall‐Keller

Druhan

et al. 2008

Cytokine

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The granulocyte colony-stimulating factor receptor (G-CSFR) is a critical regulator of granulopoiesis, but the mechanisms controlling its surface expression are poorly understood. Recent studies using transfected cell lines have suggested the activated G-CSFR is routed to the lysosome and not the proteasome. Here, we examined the role of the ubiquitin/proteasome system in regulating G-CSFR surface expression in both ts20 cells that have a temperature-sensitive E1 ubiquitinactivating enzyme and in primary human neutrophils. We show that the G-CSFR is constitutively ubiquitinated, which increases following ligand binding. In the absence of a functional E1 enzyme, ligand-induced internalization of the receptor is inhibited. Pre-treatment of ts20 transfectants with either chloroquine or MG132 inhibited ligand-induced G-CSFR degradation, suggesting a role for both lysosomes and proteasomes in regulating G-CSFR surface expression in this cell line. In neutrophils, inhibition of the proteasome but not the lysosome was found to inhibit internalization/ degradation of the activated G-CSFR. Collectively, these data demonstrate the requirement for a functional ubiquitin/proteasome system in G-CSFR internalization and degradation. Our results suggest a prominent role for the proteasome in physiologic modulation of the G-CSFR, and provide further evidence for the importance of the ubiquitin/proteasome system in the initiation of negative signaling by cytokine receptors.

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Section: Discussionmentioning

confidence: 99%

Role of the proteasome in modulating native G-CSFR expression

Kindwall‐Keller

Druhan

et al. 2008

Cytokine

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“…Recently, De Lau et al (1998) identi®ed the granulocyte colony stimulating factor receptor gene (G-CSFR) as induced in a non-t(1;19) cell line coincident with activation of E2a-Pbx1 expression and as consistently upregulated in t(1;19)-containing leukemias. We did not identify cDNA fragments encoding G-CSFR, potentially due to its low expression level, to negative selection by our RDA protocol, or to the selective ampli®cation of other more abundant sequences representing dierences between Nalm-6 (t(1;19)-negative) and 697 (t(1;19)-positive) pre-B cells.…”

Section: Discussionmentioning

confidence: 99%

EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1

McGrath

Pasillas

et al. 1999

Oncogene

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“…A number of studies have also described a role for altered G-CSF-R signalling as a contributing factor to a range of hematological malignancies. For example, expression of the CSF3R gene is increased by two oncogenic fusions, directly in the case of E2A-Pbx1 (96), or indirectly (via C/EBPε) by AML1-MTG8 (97). In the latter case, this lead to increased G-CSF-dependent proliferation (97).…”

Section: Indirect Involvement Of the G-csf-r In Diseasementioning

confidence: 99%

The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease

Ward

2007

Front Biosci

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Granulocyte colony-stimulating factor (G-CSF) is a key regulator of granulopoiesis via stimulation of a specific cell-surface receptor, the G-CSF-R, found on hematopoietic progenitor cells as well as neutrophilic granulocytes. It is perhaps not surprising, therefore, that mutations of the G-CSF-R has been implicated in several clinical settings that affect granulocytic differentiation, particularly severe congenital neutropenia, myelodysplastic syndrome and acute myeloid leukemia. However, other studies suggest that signalling via the G-CSF-R is also involved in a range of other malignancies. This review focuses on the molecular mechanisms through which the G-CSF-R contributes to disease.

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The gene encoding the granulocyte colony-stimulating factor receptor is a target for deregulation in pre-B ALL by the t(1;19)-specific oncoprotein E2A-Pbx1

Cited by 19 publications

References 24 publications

Role of the proteasome in modulating native G-CSFR expression

Role of the proteasome in modulating native G-CSFR expression

EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1

The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease

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