 |
English
|
正體中文
|
简体中文
|
Items with full text/Total items : 12145/12927 (94%)
Visitors : 911289
Online Users : 912
|
|
|
Loading...
|
Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/3539
|
| Title: | The M type K15 protein of Kaposi's sarcoma-associated herpesvirus regulates microRNA expression via its SH2-binding motif to induce cell migration and invasion |
| Authors: | Tsai, YH;Wu, MF;Wu, YH;Chang, SJ;Lin, SF;Sharp, TV;Wang, HW |
| Contributors: | Division of Clinical Research |
| Abstract: | Kaposi's sarcoma (KS) associated herpesvirus (KSHV) is the etiological agent of KS. In vivo, KS is a tumor capable of spreading throughout the body, and pulmonary metastasis is observed clinically. In vitro, KSHV induces the invasiveness of endothelial cells. The KSHV open reading frame K15 is a KSHV-specific gene encoding a transmembrane protein. Two highly divergent forms of K15, the predominant (P) and minor (M) forms (K15P and K15M, respectively), have been identified in different KSHV strains. The two K15 alleles resemble the latent membrane protein 2A (LMP2A) gene of Epstein-Barr virus (EBV) in their genomic locations and protein topology. Also, both K15 proteins have motifs similar to those found in the EBV LMP1 protein. K15 therefore appears to be a hybrid of a distant evolutionary relative of EBV LMP1 and LMP2A. Since both LMP1 and LMP2A proteins are capable of inducing cell motility, we sought to determine whether K15 has similar abilities. In this study, we show that K15M is latently expressed in KSHV-positive PEL cells and knockdown of K15M in PEL cells reduces cell motility. K15M localizes to lysosomal membranes and induces cell migration, invasion, and NF-κB (but not AP-1) activity via its conserved SH2-binding motif. K15M also induces the expression of microRNAs miR-21 and miR-31 via this conserved motif, and knocking down both these microRNAs eliminates K15M-induced cell motility. Therefore, K15M may contribute to KSHV-mediated tumor metastasis and angiogenesis via regulation of miR-21 and miR-31, which we show here for the first time to be a specific regulator of cell migration. In light of these findings, the targeting of K15 or the downstream microRNAs regulated by it may represent novel therapies for treatment of KSHV-associated neoplasia. |
| Date: | 2009-01 |
| Relation: | Journal of Virology. 2009 Jan;83(2):622-632. |
| Link to: | http://dx.doi.org/10.1128/jvi.00869-08 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-538X&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000262045000012 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=58149502550 |
| Appears in Collections: | [林素芳] 期刊論文
|
Files in This Item:
| File |
Description |
Size | Format | |
|---|
| SCP58149502550.pdf | | 2457Kb | Adobe PDF | 1109 | View/Open |
|
All items in NHRI are protected by copyright, with all rights reserved.
|
