The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype
Chromosomal translocations involving the nucleoporin <i>NUP98</i> gene are recurrently identified in leukemia; yet, the cellular defects accompanying NUP98 fusion proteins are poorly characterized. NUP98 fusions cause changes in nuclear and nuclear envelope (NE) organization, in particul...
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MDPI AG
2021-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/2851 |
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| author | Marcela Vaz Birthe Fahrenkrog |
| author_facet | Marcela Vaz Birthe Fahrenkrog |
| author_sort | Marcela Vaz |
| collection | DOAJ |
| description | Chromosomal translocations involving the nucleoporin <i>NUP98</i> gene are recurrently identified in leukemia; yet, the cellular defects accompanying NUP98 fusion proteins are poorly characterized. NUP98 fusions cause changes in nuclear and nuclear envelope (NE) organization, in particular, in the nuclear lamina and the lamina associated polypeptide 2α (LAP2α), a regulator of the tumor suppressor retinoblastoma protein (RB). We demonstrate that, for NUP98-HOXA9 (NHA9), the best-studied NUP98 fusion protein, its effect(s) on nuclear architecture largely depend(s) on RB. Morphological alterations caused by the expression of NHA9 are largely diminished in the absence of RB, both in human cells expressing the human papillomavirus 16 E7 protein and in mouse embryonic fibroblasts lacking RB. We further show that NHA9 expression associates with distinct histone modification. Moreover, the pattern of trimethylation of histone H3 lysine-27 is affected by NHA9, again in an RB-dependent manner. Our results pinpoint to an unexpected interplay between NUP98 fusion proteins and RB, which may contribute to leukemogenesis. |
| first_indexed | 2024-03-10T05:37:42Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:37:42Z |
| publishDate | 2021-10-01 |
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| series | Cells |
| spelling | doaj.art-bf8ef75798a148e086d06304af3e71d32023-11-22T22:47:40ZengMDPI AGCells2073-44092021-10-011011285110.3390/cells10112851The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope PhenotypeMarcela Vaz0Birthe Fahrenkrog1Laboratory Biologie du Noyau, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, 6041 Charleroi, BelgiumLaboratory Biologie du Noyau, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, 6041 Charleroi, BelgiumChromosomal translocations involving the nucleoporin <i>NUP98</i> gene are recurrently identified in leukemia; yet, the cellular defects accompanying NUP98 fusion proteins are poorly characterized. NUP98 fusions cause changes in nuclear and nuclear envelope (NE) organization, in particular, in the nuclear lamina and the lamina associated polypeptide 2α (LAP2α), a regulator of the tumor suppressor retinoblastoma protein (RB). We demonstrate that, for NUP98-HOXA9 (NHA9), the best-studied NUP98 fusion protein, its effect(s) on nuclear architecture largely depend(s) on RB. Morphological alterations caused by the expression of NHA9 are largely diminished in the absence of RB, both in human cells expressing the human papillomavirus 16 E7 protein and in mouse embryonic fibroblasts lacking RB. We further show that NHA9 expression associates with distinct histone modification. Moreover, the pattern of trimethylation of histone H3 lysine-27 is affected by NHA9, again in an RB-dependent manner. Our results pinpoint to an unexpected interplay between NUP98 fusion proteins and RB, which may contribute to leukemogenesis.https://www.mdpi.com/2073-4409/10/11/2851NUP98-HOXA9retinoblastomanuclear envelopePcGhistones |
| spellingShingle | Marcela Vaz Birthe Fahrenkrog The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype Cells NUP98-HOXA9 retinoblastoma nuclear envelope PcG histones |
| title | The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype |
| title_full | The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype |
| title_fullStr | The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype |
| title_full_unstemmed | The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype |
| title_short | The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype |
| title_sort | retinoblastoma tumor suppressor is required for the nup98 hoxa9 induced aberrant nuclear envelope phenotype |
| topic | NUP98-HOXA9 retinoblastoma nuclear envelope PcG histones |
| url | https://www.mdpi.com/2073-4409/10/11/2851 |
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