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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Autores principales:	Marcela Vaz, Birthe Fahrenkrog
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	NUP98-HOXA9 retinoblastoma nuclear envelope PcG histones Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bf8ef75798a148e086d06304af3e71d3
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spelling	oai:doaj.org-article:bf8ef75798a148e086d06304af3e71d32021-11-25T17:07:59ZThe Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype10.3390/cells101128512073-4409https://doaj.org/article/bf8ef75798a148e086d06304af3e71d32021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2851https://doaj.org/toc/2073-4409Chromosomal 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.Marcela VazBirthe FahrenkrogMDPI AGarticleNUP98-HOXA9retinoblastomanuclear envelopePcGhistonesBiology (General)QH301-705.5ENCells, Vol 10, Iss 2851, p 2851 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NUP98-HOXA9 retinoblastoma nuclear envelope PcG histones Biology (General) QH301-705.5
spellingShingle	NUP98-HOXA9 retinoblastoma nuclear envelope PcG histones Biology (General) QH301-705.5 Marcela Vaz Birthe Fahrenkrog The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype
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.
format	article
author	Marcela Vaz Birthe Fahrenkrog
author_facet	Marcela Vaz Birthe Fahrenkrog
author_sort	Marcela Vaz
title	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_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_sort	retinoblastoma tumor suppressor is required for the nup98-hoxa9-induced aberrant nuclear envelope phenotype
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bf8ef75798a148e086d06304af3e71d3
work_keys_str_mv	AT marcelavaz theretinoblastomatumorsuppressorisrequiredforthenup98hoxa9inducedaberrantnuclearenvelopephenotype AT birthefahrenkrog theretinoblastomatumorsuppressorisrequiredforthenup98hoxa9inducedaberrantnuclearenvelopephenotype AT marcelavaz retinoblastomatumorsuppressorisrequiredforthenup98hoxa9inducedaberrantnuclearenvelopephenotype AT birthefahrenkrog retinoblastomatumorsuppressorisrequiredforthenup98hoxa9inducedaberrantnuclearenvelopephenotype
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The Retinoblastoma Tumor Suppressor Is Required for the NUP98-HOXA9-Induced Aberrant Nuclear Envelope Phenotype

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