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-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.
Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China.
Junhu
J
Wan
Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China.
Weizhi
W
Xu
Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China.
Jun
J
Zhan
Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China.
Ji
J
Ma
Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China.
Xueying
X
Li
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yuping
Y
Xie
Department of Radiation Medicine, Peking University Health Science Center, Beijing 100191, China.
Jiadong
J
Wang
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
Wei-Guo
WG
Zhu
Department of Medical Genetics, Peking University Health Science Center, Beijing 100191, China.
Jianyuan
J
Luo
Department of Anatomy, Histology and Embryology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China Hongquan.Zhang@bjmu.edu.cn.
Hongquan
H
Zhang
D000072283:A549 Cells; D000107:Acetylation; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011499:Protein Processing, Post-Translational; D056564:Sirtuin 1 / Q000378:metabolism; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000502:physiology*; D000099224:p300-CBP-Associated Factor
D018398:Homeodomain Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; D056564:Sirtuin 1; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C491257:HOXB9 protein, human; C498707:JMJD6 protein, human; C447939:SIRT1 protein, human