ARHI (DIRAS3), an imprinted tumour suppressor gene, binds to importins and blocks nuclear import of cargo proteins

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	ARHI (DIRAS3), an imprinted tumour suppressor gene, binds to importins and blocks nuclear import of cargo proteins
	Huang, S. Y. ; Chang, I. S. ; Lin, W. B. ; Ye, W. D. ; Luo, R. Z. ; Lu, Z. ; Lu, Y. L. ; Zhang, K. ; Liao, W. S. L. ; Tao, T. ; Bast, R. C. ; Chen, X. M. ; Yu, Y. H. ; Tao T(陶涛)
刊名	http://dx.doi.org/10.1042/BSR20090008
	2010-06
关键词	OVARIAN-CANCER CELLS GLUCOCORTICOID-RECEPTOR SIGNAL TRANSDUCERS TRANSPORT STAT3 BREAST BETA PHOSPHORYLATION TRANSCRIPTION-3 TRANSLOCATION
英文摘要	National Cancer Institute [CA 80957, CA 64602, GM68556]; National Foundation for Cancer Research [LF 2004-00009224HM]; National Natural Science Foundation of China [3047085, 90608007]; Ministry of Science and Technology of China [2006AA02A310]; ARHI (aplasia Ras homologue member I; also known as DIRAS3) is an imprinted tumour suppressor gene, the expression of which is lost in the majority of breast and ovarian cancers. Unlike its homologues Ras and Rap, ARHI functions as a tumour suppressor. Our previous study showed that ARHI can interact with the transcriptional activator STAT3 (signal transducer and activator of transcription 3) and inhibit its nuclear translocation in human breast- and ovarian-cancer cells. To identify proteins that interact with ARHI in nuclear translocation, in the present study, we performed proteomic analysis and identified several importins that can associate with ARHI. To further explore this novel finding, we purified 10 GST (glutathione transferase) importin fusion proteins (importins 7, 8, 13, beta 1, alpha 1, alpha 3, alpha 5, alpha 6, alpha 7 and mutant alpha 1). Using a GST-pulldown assay, we found that ARHI can bind strongly to most importins; however, its binding is markedly reduced with an importin alpha 1 mutant that contains an altered NLS (nuclear-localization signal) domain. In addition, an ARHI N-terminal deletion mutant exhibits greatly reduced binding to all importins compared with wild-type ARHI. In nuclear-import assays, the addition of ARHI blocked nuclear localization of phosphorylated STAT3. ARHI also inhibits the interaction of Ran importin complexes with GFP (green fluorescent protein) fusion proteins that contain an NLS domain and a beta-like import receptor-binding domain, thereby blocking their nuclear localization. By conducting GST-pulldown assays, we found that ARHI could compete for Ranimportin binding. Thus ARHI-induced disruption of importin-binding to cargo proteins, including STAT3, could serve as an important regulatory mechanism that contributes to the tumour-suppressor function of ARHI.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65706]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Huang, S. Y.,Chang, I. S.,Lin, W. B.,et al. ARHI (DIRAS3), an imprinted tumour suppressor gene, binds to importins and blocks nuclear import of cargo proteins[J]. http://dx.doi.org/10.1042/BSR20090008,2010.
APA	Huang, S. Y..,Chang, I. S..,Lin, W. B..,Ye, W. D..,Luo, R. Z..,...&陶涛.(2010).ARHI (DIRAS3), an imprinted tumour suppressor gene, binds to importins and blocks nuclear import of cargo proteins.http://dx.doi.org/10.1042/BSR20090008.
MLA	Huang, S. Y.,et al."ARHI (DIRAS3), an imprinted tumour suppressor gene, binds to importins and blocks nuclear import of cargo proteins".http://dx.doi.org/10.1042/BSR20090008 (2010).