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Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling
Sun, X.1; Lu, B.1; Hu, B.2; Xiao, W.2; Li, W.1; Huang, Z.1; Huang, Z (reprint author), Wuhan Univ, Coll Life Sci, 16 Luo Jia Shan, Wuhan 430072, Hubei, Peoples R China.
2014-03-01
Source PublicationBLOOD CANCER JOURNAL
ISSN2044-5385
Volume4Pages:e198
Abstract12-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.; 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.
SubtypeArticle
KeywordNf-kappa-b Thrombopoietin-induced Activation K562 Cells Kinase Transcription Expression Gata-1 Cancer Pathway Megakaryopoiesis
Department[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
DOI10.1038/bcj.2014.18
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational 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] ; 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] ; 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] ; 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]
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000334494800010
WOS KeywordNF-KAPPA-B ; THROMBOPOIETIN-INDUCED ACTIVATION ; K562 CELLS ; KINASE ; TRANSCRIPTION ; EXPRESSION ; GATA-1 ; CANCER ; PATHWAY ; MEGAKARYOPOIESIS
Funding OrganizationNational 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] ; 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] ; 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] ; 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]
Citation statistics
Cited Times:16[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/20101
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorHuang, Z (reprint author), Wuhan Univ, Coll Life Sci, 16 Luo Jia Shan, Wuhan 430072, Hubei, Peoples R China.
Affiliation1.Wuhan Univ, Coll Life Sci, Wuhan 430072, Hubei, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, Wuhan, Peoples R China
Recommended Citation
GB/T 7714
Sun, X.,Lu, B.,Hu, B.,et al. Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling[J]. BLOOD CANCER JOURNAL,2014,4:e198.
APA Sun, X..,Lu, B..,Hu, B..,Xiao, W..,Li, W..,...&Huang, Z .(2014).Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling.BLOOD CANCER JOURNAL,4,e198.
MLA Sun, X.,et al."Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic megakaryocyte differentiation by modulating TPA-induced signaling".BLOOD CANCER JOURNAL 4(2014):e198.
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