| An evolutionarily conserved pten-c/ebp alpha-ctnna1 axis controls myeloid development and transformation | |
| Fu, Chun-Tang1,2,3; Zhu, Kang-Yong1,2,3; Mi, Jian-Qing1,2,3; Liu, Yuan-Fang1,2,3; Murray, Susan T.4; Fu, Yan-Fang1,2,3; Ren, Chun-Guang1,2,3; Dong, Zhi-Wei1,2,3; Liu, Yi-Jie1,2,3; Dong, Mei1,2,3 | |
| 刊名 | Blood
 |
| 2010-06-10 | |
| 卷号 | 115期号:23页码:4715-4724 |
| ISSN号 | 0006-4971 |
| DOI | 10.1182/blood-2009-11-255778 |
| 通讯作者 | Liu, ting xi(txliu@sibs.ac.cn) |
| 英文摘要 | Loss of function of tumor suppressor genes, such as pten, cebpa, and ctnna1 (encoding the alpha-catenin protein), has been found to play an essential role in leukemogenesis. however, whether these genes genetically interact remains largely unknown. here, we show that pten-mammalian target of rapamycin signaling acts upstream to dictate the ratio of wild-type p42 c/ebp alpha to its dominant-negative p30 isoform, which critically determines whether p30 c/ebp alpha (lower p42/p30 ratio) or p42 c/ebp alpha (higher p42/p30 ratio) binds to the proximal promoter of the retained ctnna1 allele. binding of p30 c/ebp alpha recruits the polycomb repressive complex 2 to suppress ctnna1 transcription through repressive h3k27me3 modification, whereas binding of p42 c/ebp alpha relieves this repression and promotes ctnna1 expression through activating h3k4me3 modification. loss of pten function in mice and zebrafish induces myelodysplasia with abnormal invasiveness of myeloid progenitors accompanied by significant reductions in both wild-type c/ebp alpha and alpha-catenin protein. importantly, frame-shift mutations in either pten or cebpa were detected exclusively in the primary lics with low ctnna1 expression. this study uncovers a novel molecular pathway, pten-c/ebp alpha-ctnna1, which is evolutionarily conserved and might be therapeutically targeted to eradicate lics with low ctnna1 expression. (blood. 2010;115(23):4715-4724) |
| WOS关键词 | LEUKEMIA-INITIATING CELLS ; HEMATOPOIETIC STEM-CELLS ; SINGLE CEBPA MUTATIONS ; GENE-EXPRESSION ; C/EBP-ALPHA ; MYELODYSPLASTIC SYNDROMES ; HUMAN CANCER ; IN-VIVO ; ZEBRAFISH ; CATENIN |
| WOS研究方向 | Hematology |
| WOS类目 | Hematology |
| 语种 | 英语 |
| 出版者 | AMER SOC HEMATOLOGY |
| WOS记录号 | WOS:000278635900018 |
| 内容类型 | 期刊论文 |
| URI标识 | http://www.corc.org.cn/handle/1471x/2408351 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Liu, Ting Xi |
| 作者单位 | 1.Chinese Acad Sci, Lab Dev & Dis, Shanghai Inst Biol Sci, Grad Sch,Inst Hlth Sci, Shanghai 200025, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Grad Sch, Key Lab Stem Cell Biol,Inst Hlth Sci, Shanghai 200025, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Grad Sch, State Key Lab Med Genom,Inst Hlth Sci, Shanghai 200025, Peoples R China 4.Univ Rochester, Div Hematol Oncol, Rochester, NY 14627 USA 5.Loyola Univ, Med Ctr, Dept Pathol, Oncol Inst,Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA 6.Shanghai Jiao Tong Univ, Sch Med, Shanghai Stem Cell Inst, Shanghai 200030, Peoples R China 7.Shanghai Univ, Model Organism Div, Inst E, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fu, Chun-Tang,Zhu, Kang-Yong,Mi, Jian-Qing,et al. An evolutionarily conserved pten-c/ebp alpha-ctnna1 axis controls myeloid development and transformation[J]. Blood,2010,115(23):4715-4724. |
| APA | Fu, Chun-Tang.,Zhu, Kang-Yong.,Mi, Jian-Qing.,Liu, Yuan-Fang.,Murray, Susan T..,...&Liu, Ting Xi.(2010).An evolutionarily conserved pten-c/ebp alpha-ctnna1 axis controls myeloid development and transformation.Blood,115(23),4715-4724. |
| MLA | Fu, Chun-Tang,et al."An evolutionarily conserved pten-c/ebp alpha-ctnna1 axis controls myeloid development and transformation".Blood 115.23(2010):4715-4724. |
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