Quercetin-induced ubiquitination and down-regulation of Her-2/neu.
Quercetin-induced ubiquitination and down-regulation of Her-2/neu.
复制标题
槲皮素引起的泛素化和HER-2/NEU的下调。
DOI：
10.1002/jcb.21859
复制
发表时间：
2008-10-01
影响因子：
4
通讯作者：
Lee, Yong J.
中科院分区：
文献类型：
--
作者：
Jeong, Jae-Hoon;An, Jee Young;Kwon, Yong Tae;Li, Lu-Yuan;Lee, Yong J.
Her-2/neu (ErbB2) is a transmembrane tyrosine kinase and acts as a co-receptor for the other EGFR family members. It is well known that high expression of Her-2/neu is associated with a poor prognosis in breast cancer. Quercetin, a flavonoid present in many vegetables and fruits, has been studied extensively as a chemoprevention agent in several cancer models. In this study, we observed that quercetin decreased the level of Her-2/neu protein in time- and dose-dependent manners and also inhibited the downstream survival PI3K-Akt signaling pathway in Her-2/neu-overexpressing breast cancer SK-Br3 cells. We also observed that quercetin induced polyubiquitination of Her-2/neu. When the proteasome pathway was blocked by MG-132 during quercetin treatment, accumulation of the NP-40 insoluble form of Her-2/neu occurred. Interestingly, data from immunocomplex studies revealed that quercetin promoted interaction between Her-2/neu and Hsp90 which is a molecular chaperone involved in stabilization of Her-2/neu. In this condition, inhibition of Hsp90 activity by a specific inhibitor, geldanamycin (GA), or intracellular ATP depletion caused dissociation of Hsp90 from Her-2/neu and promoted ubiquitination and down-regulation of Her-2/neu protein. In addition, the carboxyl terminus of Hsc70-interacting protein (CHIP), a chaperone-dependent E3 ubiquitin ligase, played a crucial role in the quercetin-induced ubiquitination of Her-2/neu. Inhibition of tyrosine kinase activity of Her-2/neu by quercetin could indicate an lateration in the Her-2/neu structure which promotes CHIP recruitments and down-regulation of Her-2/neu. We believe that by using quercetin, new therapeutic strategies can be developed to treat Her-2/neu overexpressing cancers.
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DOI：
10.1073/pnas.122249299
发表时间：
2002-06-25
影响因子：
11.1
作者：
Özcelik, C;Erdmann, B;Garratt, AN
通讯作者：
Garratt, AN
影响因子：
3.6
作者：
Jeon, Hyunchu;Kim, Heejung;Jung, Yunjin
通讯作者：
Jung, Yunjin
影响因子：
5.6
作者：
Kim, WK;Bang, MH;Park, JHY
通讯作者：
Park, JHY
DOI：
10.1016/j.bbamcr.2006.11.004
发表时间：
2007-03-01
影响因子：
5.1
作者：
Jung, Yunjin;Xu, Wanping;Neckers, Len
通讯作者：
Neckers, Len
影响因子：
64.8
作者：
MEYER, D;BIRCHMEIER, C
通讯作者：
BIRCHMEIER, C