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PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6

HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBP-associ...

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Autores principales: Wan, Junhu, Xu, Weizhi, Zhan, Jun, Ma, Ji, Li, Xueying, Xie, Yuping, Wang, Jiadong, Zhu, Wei-guo, Luo, Jianyuan, Zhang, Hongquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159546/
https://www.ncbi.nlm.nih.gov/pubmed/27613418
http://dx.doi.org/10.1093/nar/gkw808
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author Wan, Junhu
Xu, Weizhi
Zhan, Jun
Ma, Ji
Li, Xueying
Xie, Yuping
Wang, Jiadong
Zhu, Wei-guo
Luo, Jianyuan
Zhang, Hongquan
author_facet Wan, Junhu
Xu, Weizhi
Zhan, Jun
Ma, Ji
Li, Xueying
Xie, Yuping
Wang, Jiadong
Zhu, Wei-guo
Luo, Jianyuan
Zhang, Hongquan
author_sort Wan, Junhu
collection PubMed
description HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBP-associated factor (PCAF) interacts with and acetylates HOXB9 both in vivo and in vitro. Conversely, the acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found that HOXB9 is acetylated at lysine 27 (AcK27). Functionally, in contrast to the wild type HOXB9, AcK27-HOXB9 decreased its capacity in promoting lung cancer cell migration and tumor growth in mice. Mechanistically, AcK27-HOXB9 suppresses the transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by direct occupying the promoter of JMJD6 gene. For clinical relevance, elevated HOXB9 acetylation at K27 predicts a better prognosis in lung adenocarcinoma patients. Taken together, we identified the first PTM of HOXB9 by demonstrating that HOXB9 can be acetylated and AcK27-HOXB9 counteracts the role of the wild-type HOXB9 in regulating lung adenocarcinoma progression.
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spelling pubmed-51595462016-12-16 PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6 Wan, Junhu Xu, Weizhi Zhan, Jun Ma, Ji Li, Xueying Xie, Yuping Wang, Jiadong Zhu, Wei-guo Luo, Jianyuan Zhang, Hongquan Nucleic Acids Res Gene regulation, Chromatin and Epigenetics HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBP-associated factor (PCAF) interacts with and acetylates HOXB9 both in vivo and in vitro. Conversely, the acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found that HOXB9 is acetylated at lysine 27 (AcK27). Functionally, in contrast to the wild type HOXB9, AcK27-HOXB9 decreased its capacity in promoting lung cancer cell migration and tumor growth in mice. Mechanistically, AcK27-HOXB9 suppresses the transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by direct occupying the promoter of JMJD6 gene. For clinical relevance, elevated HOXB9 acetylation at K27 predicts a better prognosis in lung adenocarcinoma patients. Taken together, we identified the first PTM of HOXB9 by demonstrating that HOXB9 can be acetylated and AcK27-HOXB9 counteracts the role of the wild-type HOXB9 in regulating lung adenocarcinoma progression. Oxford University Press 2016-12-15 2016-09-08 /pmc/articles/PMC5159546/ /pubmed/27613418 http://dx.doi.org/10.1093/nar/gkw808 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Wan, Junhu
Xu, Weizhi
Zhan, Jun
Ma, Ji
Li, Xueying
Xie, Yuping
Wang, Jiadong
Zhu, Wei-guo
Luo, Jianyuan
Zhang, Hongquan
PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6
title PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6
title_full PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6
title_fullStr PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6
title_full_unstemmed PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6
title_short PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6
title_sort pcaf-mediated acetylation of transcriptional factor hoxb9 suppresses lung adenocarcinoma progression by targeting oncogenic protein jmjd6
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159546/
https://www.ncbi.nlm.nih.gov/pubmed/27613418
http://dx.doi.org/10.1093/nar/gkw808
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