Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells

	Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells
	Liu, XJ; Liu, D; Qian, DM; Dai, J; An, Y; Jiang, SY; Stanley, B; Yang, JM; Wang, B; Liu, XY
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2012
卷号	287 期号:23 页码:19599-19609
通讯作者	Liu, DX (reprint author), Penn State Coll Med, Hershey, PA 17033 USA.,dliu@psu.edu
英文摘要	Nucleophosmin (NPM1/B23) and the activating transcription factor 5 (ATF5) are both known to subject to cell type-dependent regulation. NPM1 is expressed weakly in hepatocytes and highly expressed in hepatocellular carcinomas (HCC) with a clear correlation between enhanced NPM1 expression and increased tumor grading and poor prognosis, whereas in contrast, ATF5 is expressed abundantly in hepatocytes and down-regulated in HCC. Re-expression of ATF5 in HCC inhibits cell proliferation. We report here that using an unbiased approach, tandem affinity purification (TAP) followed with mass spectrometry (MS), we identified NPM1 as a novel ATF5-interacting protein. Unlike many other NPM1-interacting proteins that interact with the N-terminal oligomerization domain of NPM1, ATF5 binds via its basic leucine zipper to the C-terminal region of NPM1 where its nucleolar localization signal is located. NPM1 association with ATF5, whose staining patterns partially overlap in the nucleoli, promotes ATF5 protein degradation through proteasome-dependent and caspase-dependent pathways. NPM1-c, a mutant NPM1 that is defective in nucleolar localization, failed to stimulate ATF5 polyubiquitination and was unable to down-regulate ATF5. NPM1 interaction with ATF5 displaces HSP70, a known ATF5-interacting protein, from ATF5 protein complexes and antagonizes its role in stabilization of ATF5 protein. NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. Our study establishes a mechanistic link between elevated NPM1 expression and depressed ATF5 in HCC and suggests that regulation of ATF5 by NPM1 plays an important role in the proliferation and survival of HCC.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	ARF TUMOR-SUPPRESSOR ; NEURAL PROGENITOR CELLS ; BREAST-CANCER CELLS ; CENTROSOME DUPLICATION ; HISTONE CHAPERONE ; GENE-EXPRESSION ; G(2)-M ARREST ; C6 GLIOMA ; TARGET ; PROLIFERATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000306411900071
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/687]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Liu, XJ,Liu, D,Qian, DM,et al. Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(23):19599-19609.
APA	Liu, XJ.,Liu, D.,Qian, DM.,Dai, J.,An, Y.,...&Liu, DX.(2012).Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells.JOURNAL OF BIOLOGICAL CHEMISTRY,287(23),19599-19609.
MLA	Liu, XJ,et al."Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells".JOURNAL OF BIOLOGICAL CHEMISTRY 287.23(2012):19599-19609.