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题名: Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling
作者: Sun, X.1; Lu, B.1; Hu, B.2; Xiao, W.2; Li, W.1; Huang, Z.1
通讯作者: Huang, Z (reprint author), Wuhan Univ, Coll Life Sci, 16 Luo Jia Shan, Wuhan 430072, Hubei, Peoples R China.
关键词: NF-KAPPA-B ; THROMBOPOIETIN-INDUCED ACTIVATION ; K562 CELLS ; KINASE ; TRANSCRIPTION ; EXPRESSION ; GATA-1 ; CANCER ; PATHWAY ; MEGAKARYOPOIESIS
刊名: BLOOD CANCER JOURNAL
发表日期: 2014-03-01
DOI: 10.1038/bcj.2014.18
卷: 4, 页:e198
收录类别: SCI
文章类型: Article
部门归属: [Sun, X.; Lu, B.; Li, W.; Huang, Z.] Wuhan Univ, Coll Life Sci, Wuhan 430072, Hubei, Peoples R China; [Hu, B.; Xiao, W.] Chinese Acad Sci, Inst Hydrobiol, Wuhan, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China [81070406, 31371481]; PhD Programs Foundation of Ministry of Education of China [20110141110016]; Program for New Century Excellent Talents in University (NCET) of the Ministry of Education of China [NCET-12-0422]; Chinese 111 project [B06018]
类目[WOS]: Oncology
研究领域[WOS]: Oncology
摘要: 12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways, alters gene expression and causes leukemic cell differentiation. How TPA-induced genes contribute to leukemic cell differentiation remains elusive. We noticed that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and its upregulation concurred with human megakaryocyte differentiation. In K562 cells, ectopic expression of C7ORF41 significantly increased CD61 expression, enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41 knockdown caused an opposite phenotype. These observations suggest that C7ORF41 may promote megakaryocyte differentiation partially through modulating ERK and JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this, C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41. Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) was the major activator of C7ORF41 that in turn repressed NF-kappa B activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse fetal liver cells impaired megakaryocyte differentiation. Taken together, we have identified the function of a novel gene C7ORF41 that forms interplaying regulatory network in TPA-induced signaling and promotes leukemic and normal megakaryocyte differentiation.
英文摘要: 12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways, alters gene expression and causes leukemic cell differentiation. How TPA-induced genes contribute to leukemic cell differentiation remains elusive. We noticed that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and its upregulation concurred with human megakaryocyte differentiation. In K562 cells, ectopic expression of C7ORF41 significantly increased CD61 expression, enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41 knockdown caused an opposite phenotype. These observations suggest that C7ORF41 may promote megakaryocyte differentiation partially through modulating ERK and JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this, C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41. Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) was the major activator of C7ORF41 that in turn repressed NF-kappa B activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse fetal liver cells impaired megakaryocyte differentiation. Taken together, we have identified the function of a novel gene C7ORF41 that forms interplaying regulatory network in TPA-induced signaling and promotes leukemic and normal megakaryocyte differentiation.
关键词[WOS]: NF-KAPPA-B ; THROMBOPOIETIN-INDUCED ACTIVATION ; K562 CELLS ; KINASE ; TRANSCRIPTION ; EXPRESSION ; GATA-1 ; CANCER ; PATHWAY ; MEGAKARYOPOIESIS
语种: 英语
WOS记录号: WOS:000334494800010
ISSN号: 2044-5385
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20101
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Wuhan Univ, Coll Life Sci, Wuhan 430072, Hubei, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, Wuhan, Peoples R China

Recommended Citation:
Sun, X.; Lu, B.; Hu, B.; Xiao, W.; Li, W.; Huang, Z..Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling,BLOOD CANCER JOURNAL,2014,4():e198
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