Cargando…
Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway
Drosophila myelodysplasia/myeloid leukemia factor (dMLF), a homolog of human MLF1, oncogene was first identified by yeast two-hybrid screen using the DNA replication-related element-binding factor (DREF) as bait. DREF is a transcription factor that regulates proliferation-related genes in Drosophila...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007195/ https://www.ncbi.nlm.nih.gov/pubmed/24752236 http://dx.doi.org/10.1038/oncsis.2014.13 |
_version_ | 1782314310948618240 |
---|---|
author | Yanai, H Yoshioka, Y Yoshida, H Nakao, Y Plessis, A Yamaguchi, M |
author_facet | Yanai, H Yoshioka, Y Yoshida, H Nakao, Y Plessis, A Yamaguchi, M |
author_sort | Yanai, H |
collection | PubMed |
description | Drosophila myelodysplasia/myeloid leukemia factor (dMLF), a homolog of human MLF1, oncogene was first identified by yeast two-hybrid screen using the DNA replication-related element-binding factor (DREF) as bait. DREF is a transcription factor that regulates proliferation-related genes in Drosophila. It is known that overexpression of dMLF in the wing imaginal discs through the engrailed-GAL4 driver causes an atrophied wing phenotype associated with the induction of apoptosis. However, the precise mechanisms involved have yet to be clarified. Here, we found the atrophied phenotype to be suppressed by loss-of-function mutation of Drosophila Jun N-terminal kinase (JNK), basket (bsk). Overexpression of dMLF induced ectopic JNK activation in the wing disc monitored with the puckered-lacZ reporter line, resulting in induction of apoptosis. The DREF-binding consensus DRE sequence could be shown to exist in the bsk promoter. Chromatin immunoprecipitation assays in S2 cells with anti-dMLF IgG and quantitative real-time PCR revealed that dMLF binds specifically to the bsk promoter region containing the DRE sequence. Furthermore, using a transient luciferase expression assay, we provide evidence that knockdown of dMLF reduced bsk gene promoter activity in S2 cells. Finally, we show that dMLF interacts with DREF in vivo. Altogether, these data indicate that dMLF acts with DREF to stimulate the bsk promoter and consequently activates the JNK pathway to promote apoptosis. |
format | Online Article Text |
id | pubmed-4007195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-40071952014-05-02 Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway Yanai, H Yoshioka, Y Yoshida, H Nakao, Y Plessis, A Yamaguchi, M Oncogenesis Original Article Drosophila myelodysplasia/myeloid leukemia factor (dMLF), a homolog of human MLF1, oncogene was first identified by yeast two-hybrid screen using the DNA replication-related element-binding factor (DREF) as bait. DREF is a transcription factor that regulates proliferation-related genes in Drosophila. It is known that overexpression of dMLF in the wing imaginal discs through the engrailed-GAL4 driver causes an atrophied wing phenotype associated with the induction of apoptosis. However, the precise mechanisms involved have yet to be clarified. Here, we found the atrophied phenotype to be suppressed by loss-of-function mutation of Drosophila Jun N-terminal kinase (JNK), basket (bsk). Overexpression of dMLF induced ectopic JNK activation in the wing disc monitored with the puckered-lacZ reporter line, resulting in induction of apoptosis. The DREF-binding consensus DRE sequence could be shown to exist in the bsk promoter. Chromatin immunoprecipitation assays in S2 cells with anti-dMLF IgG and quantitative real-time PCR revealed that dMLF binds specifically to the bsk promoter region containing the DRE sequence. Furthermore, using a transient luciferase expression assay, we provide evidence that knockdown of dMLF reduced bsk gene promoter activity in S2 cells. Finally, we show that dMLF interacts with DREF in vivo. Altogether, these data indicate that dMLF acts with DREF to stimulate the bsk promoter and consequently activates the JNK pathway to promote apoptosis. Nature Publishing Group 2014-04 2014-04-21 /pmc/articles/PMC4007195/ /pubmed/24752236 http://dx.doi.org/10.1038/oncsis.2014.13 Text en Copyright © 2014 Macmillan Publishers Limited This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Yanai, H Yoshioka, Y Yoshida, H Nakao, Y Plessis, A Yamaguchi, M Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway |
title | Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway |
title_full | Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway |
title_fullStr | Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway |
title_full_unstemmed | Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway |
title_short | Drosophila myeloid leukemia factor acts with DREF to activate the JNK signaling pathway |
title_sort | drosophila myeloid leukemia factor acts with dref to activate the jnk signaling pathway |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007195/ https://www.ncbi.nlm.nih.gov/pubmed/24752236 http://dx.doi.org/10.1038/oncsis.2014.13 |
work_keys_str_mv | AT yanaih drosophilamyeloidleukemiafactoractswithdreftoactivatethejnksignalingpathway AT yoshiokay drosophilamyeloidleukemiafactoractswithdreftoactivatethejnksignalingpathway AT yoshidah drosophilamyeloidleukemiafactoractswithdreftoactivatethejnksignalingpathway AT nakaoy drosophilamyeloidleukemiafactoractswithdreftoactivatethejnksignalingpathway AT plessisa drosophilamyeloidleukemiafactoractswithdreftoactivatethejnksignalingpathway AT yamaguchim drosophilamyeloidleukemiafactoractswithdreftoactivatethejnksignalingpathway |