The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation.
PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic prog...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4131979?pdf=render |
| _version_ | 1819011808303775744 |
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| author | Xi Liu Hao Yuan Laurent Peres Saijuan Chen Zhu Chen Hugues de The Jun Zhou Jun Zhu |
| author_facet | Xi Liu Hao Yuan Laurent Peres Saijuan Chen Zhu Chen Hugues de The Jun Zhou Jun Zhu |
| author_sort | Xi Liu |
| collection | DOAJ |
| description | PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colony formation. Further experiments showed that DNA-binding-defective PML/RARA mutants could not repress the transcription of retinoic acid regulated genes. Intriguingly, there were no significant differences of the micro-speckled intracellular distribution between the mutants and wild-type PML/RARA. Some retinoic acid target genes regulated by PML/RARA are involved in not only differentiation block but also hematopoietic cell self-renewal. Altogether, our data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize hematopoietic cells, while disruption of PML-nuclear body does not seem to be a prerequisite for hematopoietic cell transformation. |
| first_indexed | 2024-12-21T01:34:02Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T01:34:02Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-5400201927694875b1ada53a652451822022-12-21T19:20:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10490610.1371/journal.pone.0104906The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation.Xi LiuHao YuanLaurent PeresSaijuan ChenZhu ChenHugues de TheJun ZhouJun ZhuPML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colony formation. Further experiments showed that DNA-binding-defective PML/RARA mutants could not repress the transcription of retinoic acid regulated genes. Intriguingly, there were no significant differences of the micro-speckled intracellular distribution between the mutants and wild-type PML/RARA. Some retinoic acid target genes regulated by PML/RARA are involved in not only differentiation block but also hematopoietic cell self-renewal. Altogether, our data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize hematopoietic cells, while disruption of PML-nuclear body does not seem to be a prerequisite for hematopoietic cell transformation.http://europepmc.org/articles/PMC4131979?pdf=render |
| spellingShingle | Xi Liu Hao Yuan Laurent Peres Saijuan Chen Zhu Chen Hugues de The Jun Zhou Jun Zhu The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation. PLoS ONE |
| title | The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation. |
| title_full | The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation. |
| title_fullStr | The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation. |
| title_full_unstemmed | The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation. |
| title_short | The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation. |
| title_sort | dna binding property of pml rara but not the integrity of pml nuclear bodies is indispensable for leukemic transformation |
| url | http://europepmc.org/articles/PMC4131979?pdf=render |
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