Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible plscr1-expressing leukemic cells | |
Huang, Y.; Zhao, Q.; Zhou, C-X; Gu, Z-M; Li, D.; Xu, H-Z; Sims, P. J.; Zhao, K-W; Chen, G-Q | |
刊名 | Oncogene |
2006-10-01 | |
卷号 | 25期号:50页码:6618-6627 |
关键词 | Plscr1 Proliferation Differentiation Apoptosis Leukemia Gene regulation |
ISSN号 | 0950-9232 |
DOI | 10.1038/sj.onc.1209677 |
通讯作者 | Chen, g-q(chengq@shsmu.edu.cn) |
英文摘要 | Phospholipid scramblase 1 (plscr1) is a multiply palmitoylated protein which is localized in either the cell membrane or nucleus depending on its palmitoylated state. the increasing evidence showed the biological roles of plscr1 in cell signaling, maturation and apoptosis. to investigate the functions of plscr1 in leukemic cells, we generated an inducible plscr1-expressing cell line using myeloid leukemic u937 cells. in this cell line, plscr1 was tightly regulated and induced upon tetracycline withdrawal. our results showed that inducible plscr1 expression arrested the proliferation of u937 cells at g(1) phase. meanwhile, plscr1-overexpressing u937 cells also underwent granulocyte-like differentiation with increased sensitivity to etoposide-induced apoptosis. furthermore, we also found that plscr1 induction increased cyclin-dependent kinase inhibitors p27(kip1) and p21(cip1) proteins, together with downregulation of s phase kinase-associated protein 2 (skp2), an f-box subunit of the ubiquitin-ligase complex that targets proteins for degradation. additionally, plscr1 induction significantly decreased c-myc protein and antiapoptotic bcl-2 protein. although the exact mechanism by which plscr1 regulates these cellular events and gene expression remains unresolved, our results suggest that plscr1 plays the antagonistic role regarding leukemia development. these data will shed new insights into understanding the biochemical and biological functions of plscr1 protein. |
WOS关键词 | KINASE-C-DELTA ; GROWTH-FACTOR RECEPTOR ; UV-INDUCED APOPTOSIS ; PLASMA-MEMBRANE ; MYELOID-LEUKEMIA ; RETINOIC ACID ; C/EBP-ALPHA ; INDUCED-DIFFERENTIATION ; TRANSBILAYER MOVEMENT ; MEDIATED DEGRADATION |
WOS研究方向 | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
WOS类目 | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
语种 | 英语 |
出版者 | NATURE PUBLISHING GROUP |
WOS记录号 | WOS:000241569700006 |
内容类型 | 期刊论文 |
URI标识 | http://www.corc.org.cn/handle/1471x/2379386 |
专题 | 中国科学院大学 |
通讯作者 | Chen, G-Q |
作者单位 | 1.Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis Chinese Min, Dept Pathophysiol, Shanghai 200025, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Shanghai Inst Biol Sci, Shanghai 200030, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Med, Grad Sch, Chinese Acad Sci, Shanghai 200030, Peoples R China 4.Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA |
推荐引用方式 GB/T 7714 | Huang, Y.,Zhao, Q.,Zhou, C-X,et al. Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible plscr1-expressing leukemic cells[J]. Oncogene,2006,25(50):6618-6627. |
APA | Huang, Y..,Zhao, Q..,Zhou, C-X.,Gu, Z-M.,Li, D..,...&Chen, G-Q.(2006).Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible plscr1-expressing leukemic cells.Oncogene,25(50),6618-6627. |
MLA | Huang, Y.,et al."Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible plscr1-expressing leukemic cells".Oncogene 25.50(2006):6618-6627. |
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