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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3694108?pdf=render |
| _version_ | 1818272118834462720 |
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| author | Nayan J Sarma Nabeel R Yaseen |
| author_facet | Nayan J Sarma Nabeel R Yaseen |
| author_sort | Nayan J Sarma |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T21:36:59Z |
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| id | doaj.art-934c6b9a1c84463ab2157dfd02ea5d95 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T21:36:59Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-934c6b9a1c84463ab2157dfd02ea5d952022-12-22T00:11:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6703210.1371/journal.pone.0067032Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins.Nayan J SarmaNabeel R YaseenThe 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.http://europepmc.org/articles/PMC3694108?pdf=render |
| spellingShingle | Nayan J Sarma Nabeel R Yaseen Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3694108?pdf=render |
| work_keys_str_mv | AT nayanjsarma dyneinlightchain1dynlt1interactswithnormalandoncogenicnucleoporins AT nabeelryaseen dyneinlightchain1dynlt1interactswithnormalandoncogenicnucleoporins |