期刊
MOLECULAR CELL
卷 43, 期 1, 页码 45-56出版社
CELL PRESS
DOI: 10.1016/j.molcel.2011.05.014
关键词
-
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- Princess Margaret Hospital Foundation
- Ontario Ministry of Health and Long-Term Care
- Canadian Institutes for Health Research
- [R37CA39152]
- Grants-in-Aid for Scientific Research [22114002, 22700877, 22240085, 22114001, 20114006] Funding Source: KAKEN
Deregulation of SHP2 is associated with malignant diseases as well as developmental disorders. Although SHP2 is required for full activation of RAS signaling, other potential roles in cell physiology have not been elucidated. Here we show that SHP2 dephosphorylates parafibromin/Cdc73, a core component of the RNA polymerase II-associated factor (PAF) complex. Parafibromin is known to act as a tumor suppressor that inhibits cyclin D1 and c-myc by recruiting SUV39H1 histone methyltransferase. However, parafibromin can also act in the opposing direction by binding beta-catenin, thereby activating promitogenic/oncogenic Wnt signaling. We found that, on tyrosine dephosphorylation by SHP2, parafibromin acquires the ability to stably bind beta-catenin. The parafibromin/beta-catenin interaction overrides parafibromin/SUV39H1-mediated transrepression and induces expression of Wnt target genes, including cyclin D1 and c-myc. Hence, SHP2 governs the opposing functions of parafibromin, deregulation of which may cause the development of tumors or developmental malformations.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据