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Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins

The chimeric oncoprotein NUP98-HOXA9 results from the t(7;11)(p15;p15) chromosomal translocation and is associated with acute myeloid leukemia. It causes aberrant gene regulation and leukemic transformation through mechanisms that are not fully understood. NUP98-HOXA9 consists of an N-terminal porti...

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Autores principales: Sarma, Nayan J., Yaseen, Nabeel R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694108/
https://www.ncbi.nlm.nih.gov/pubmed/23840580
http://dx.doi.org/10.1371/journal.pone.0067032
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author Sarma, Nayan J.
Yaseen, Nabeel R.
author_facet Sarma, Nayan J.
Yaseen, Nabeel R.
author_sort Sarma, Nayan J.
collection PubMed
description The chimeric oncoprotein NUP98-HOXA9 results from the t(7;11)(p15;p15) chromosomal translocation and is associated with acute myeloid leukemia. It causes aberrant gene regulation and leukemic transformation through mechanisms that are not fully understood. NUP98-HOXA9 consists of an N-terminal portion of the nucleoporin NUP98 that contains many FG repeats fused to the DNA-binding homeodomain of HOXA9. We used a Cytotrap yeast two-hybrid assay to identify proteins that interact with NUP98-HOXA9. We identified Dynein Light Chain 1 (DYNLT1), an integral 14 KDa protein subunit of the large microtubule-based cytoplasmic dynein complex, as an interaction partner of NUP98-HOXA9. Binding was confirmed by in vitro pull down and co-immunoprecipitation assays and the FG repeat region of NUP98-HOXA9 was shown to be essential for the interaction. RNAi-mediated knockdown of DYNLT1 resulted in reduction of the ability of NUP98-HOXA9 to activate transcription and also inhibited the ability of NUP98-HOXA9 to induce proliferation of primary human hematopoietic CD34+ cells. DYNLT1 also showed a strong interaction with wild-type NUP98 and other nucleoporins containing FG repeats. Immunofluorescence analysis showed that DYNLT1 localizes primarily to the nuclear periphery, where it co-localizes with the nuclear pore complex, and to the cytoplasm. Deletion studies showed that the interactions of the nucleoporins with DYNLT1 are dependent predominantly on the C-terminal half of the DYNLT1. These data show for the first time that DYNLT1 interacts with nucleoporins and plays a role in the dysregulation of gene expression and induction of hematopoietic cell proliferation by the leukemogenic nucleoporin fusion, NUP98-HOXA9.
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spelling pubmed-36941082013-07-09 Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins Sarma, Nayan J. Yaseen, Nabeel R. PLoS One Research Article The chimeric oncoprotein NUP98-HOXA9 results from the t(7;11)(p15;p15) chromosomal translocation and is associated with acute myeloid leukemia. It causes aberrant gene regulation and leukemic transformation through mechanisms that are not fully understood. NUP98-HOXA9 consists of an N-terminal portion of the nucleoporin NUP98 that contains many FG repeats fused to the DNA-binding homeodomain of HOXA9. We used a Cytotrap yeast two-hybrid assay to identify proteins that interact with NUP98-HOXA9. We identified Dynein Light Chain 1 (DYNLT1), an integral 14 KDa protein subunit of the large microtubule-based cytoplasmic dynein complex, as an interaction partner of NUP98-HOXA9. Binding was confirmed by in vitro pull down and co-immunoprecipitation assays and the FG repeat region of NUP98-HOXA9 was shown to be essential for the interaction. RNAi-mediated knockdown of DYNLT1 resulted in reduction of the ability of NUP98-HOXA9 to activate transcription and also inhibited the ability of NUP98-HOXA9 to induce proliferation of primary human hematopoietic CD34+ cells. DYNLT1 also showed a strong interaction with wild-type NUP98 and other nucleoporins containing FG repeats. Immunofluorescence analysis showed that DYNLT1 localizes primarily to the nuclear periphery, where it co-localizes with the nuclear pore complex, and to the cytoplasm. Deletion studies showed that the interactions of the nucleoporins with DYNLT1 are dependent predominantly on the C-terminal half of the DYNLT1. These data show for the first time that DYNLT1 interacts with nucleoporins and plays a role in the dysregulation of gene expression and induction of hematopoietic cell proliferation by the leukemogenic nucleoporin fusion, NUP98-HOXA9. Public Library of Science 2013-06-26 /pmc/articles/PMC3694108/ /pubmed/23840580 http://dx.doi.org/10.1371/journal.pone.0067032 Text en © 2013 Sarma, Yaseen http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sarma, Nayan J.
Yaseen, Nabeel R.
Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins
title Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins
title_full Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins
title_fullStr Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins
title_full_unstemmed Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins
title_short Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins
title_sort dynein light chain 1 (dynlt1) interacts with normal and oncogenic nucleoporins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694108/
https://www.ncbi.nlm.nih.gov/pubmed/23840580
http://dx.doi.org/10.1371/journal.pone.0067032
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