The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia.
The antioxidant peroxiredoxin (PRDX) protein family comprises 6 members, which are implicated in a variety of cellular responses, including growth factor signal transduction. PRDX4 resides in the endoplasmic reticulum (ER), where it locally controls oxidative stress by reducing H(2)O(2) levels. We r...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3024432?pdf=render |
| _version_ | 1811218847645040640 |
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| author | Karishma K Palande Renee Beekman Lotte E van der Meeren H Berna Beverloo Peter J M Valk Ivo P Touw |
| author_facet | Karishma K Palande Renee Beekman Lotte E van der Meeren H Berna Beverloo Peter J M Valk Ivo P Touw |
| author_sort | Karishma K Palande |
| collection | DOAJ |
| description | The antioxidant peroxiredoxin (PRDX) protein family comprises 6 members, which are implicated in a variety of cellular responses, including growth factor signal transduction. PRDX4 resides in the endoplasmic reticulum (ER), where it locally controls oxidative stress by reducing H(2)O(2) levels. We recently provided evidence for a regulatory function of PRDX4 in signal transduction from a myeloid growth factor receptor, the granulocyte colony-stimulating factor receptor (G-CSFR). Upon activation, the ligand-induced G-CSFR undergoes endocytosis and routes via the early endosomes where it physically interacts with ER-resident PRDX4. PRDX4 negatively regulates G-CSFR mediated signaling. Here, we investigated whether PRDX4 is affected in acute myeloid leukemia (AML); genomic alterations and expression levels of PRDX4 were investigated. We show that genomic abnormalities involving PRDX4 are rare in AML. However, we find a strong reduction in PRDX4 expression levels in acute promyelocytic leukemia (APL) compared to normal promyelocytes and different molecular subtypes of AML. Subsequently, the possible role of DNA methylation and histone modifications in silencing of PRDX4 in APLs was investigated. We show that the reduced expression is not due to methylation of the CpG island in the promoter region of PRDX4 but correlates with increased trimethylation of histone 3 lysine residue 27 (H3K27me3) and lysine residue 4 (H3K4me3) at the transcriptional start site (TSS) of PRDX4, indicative of a bivalent histone code involved in transcriptional silencing. These findings suggest that the control of G-CSF responses by the antioxidant protein PRDX4 may be perturbed in APL. |
| first_indexed | 2024-04-12T07:15:12Z |
| format | Article |
| id | doaj.art-aa86a339bdfb4e6aa17eb5b9f976f862 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T07:15:12Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-aa86a339bdfb4e6aa17eb5b9f976f8622022-12-22T03:42:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1634010.1371/journal.pone.0016340The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia.Karishma K PalandeRenee BeekmanLotte E van der MeerenH Berna BeverlooPeter J M ValkIvo P TouwThe antioxidant peroxiredoxin (PRDX) protein family comprises 6 members, which are implicated in a variety of cellular responses, including growth factor signal transduction. PRDX4 resides in the endoplasmic reticulum (ER), where it locally controls oxidative stress by reducing H(2)O(2) levels. We recently provided evidence for a regulatory function of PRDX4 in signal transduction from a myeloid growth factor receptor, the granulocyte colony-stimulating factor receptor (G-CSFR). Upon activation, the ligand-induced G-CSFR undergoes endocytosis and routes via the early endosomes where it physically interacts with ER-resident PRDX4. PRDX4 negatively regulates G-CSFR mediated signaling. Here, we investigated whether PRDX4 is affected in acute myeloid leukemia (AML); genomic alterations and expression levels of PRDX4 were investigated. We show that genomic abnormalities involving PRDX4 are rare in AML. However, we find a strong reduction in PRDX4 expression levels in acute promyelocytic leukemia (APL) compared to normal promyelocytes and different molecular subtypes of AML. Subsequently, the possible role of DNA methylation and histone modifications in silencing of PRDX4 in APLs was investigated. We show that the reduced expression is not due to methylation of the CpG island in the promoter region of PRDX4 but correlates with increased trimethylation of histone 3 lysine residue 27 (H3K27me3) and lysine residue 4 (H3K4me3) at the transcriptional start site (TSS) of PRDX4, indicative of a bivalent histone code involved in transcriptional silencing. These findings suggest that the control of G-CSF responses by the antioxidant protein PRDX4 may be perturbed in APL.http://europepmc.org/articles/PMC3024432?pdf=render |
| spellingShingle | Karishma K Palande Renee Beekman Lotte E van der Meeren H Berna Beverloo Peter J M Valk Ivo P Touw The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia. PLoS ONE |
| title | The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia. |
| title_full | The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia. |
| title_fullStr | The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia. |
| title_full_unstemmed | The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia. |
| title_short | The antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia. |
| title_sort | antioxidant protein peroxiredoxin 4 is epigenetically down regulated in acute promyelocytic leukemia |
| url | http://europepmc.org/articles/PMC3024432?pdf=render |
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