Xianbo Lv

Publications (3)14.32 Total impact

• Article: The N-terminal phosphodegron targets TAZ/WWTR1 protein for SCFβ-TrCP-dependent degradation in response to phosphatidylinositol 3-kinase inhibition.

  Wei Huang, Xianbo Lv, Chenying Liu, Zhengyu Zha, Heng Zhang, Ying Jiang, Yue Xiong, Qun-Ying Lei, Kun-Liang Guan
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  ABSTRACT: The Hippo tumor suppressor pathway plays a major role in development and organ size control, and its dysregulation contributes to tumorigenesis. TAZ (transcriptional co-activator with PDZ-binding motif; also known as WWTR1) is a transcription co-activator acting downstream of the Hippo pathway, and increased TAZ protein levels have been associated with human cancers, such as breast cancer. Previous studies have shown that TAZ is inhibited by large tumor suppressor (LATS)-dependent phosphorylation, leading to cytoplasmic retention and ubiquitin-dependent degradation. The LATS kinase, a core component of the Hippo pathway, phosphorylates the C-terminal phosphodegron in TAZ to promote its degradation. In this study, we have found that the N-terminal phosphodegron of TAZ also plays a role in TAZ protein level regulation, particularly in response to different status of cellular PI3K signaling. GSK3, which can be inhibited by high PI3K via AKT-dependent inhibitory phosphorylation, phosphorylates the N-terminal phosphodegron in TAZ, and the phosphorylated TAZ binds to β-TrCP subunit of the SCF(β-TrCP) E3 ubiquitin ligase, thereby leading to TAZ ubiquitylation and degradation. We observed that the TAZ protein level is elevated in tumor cells with high PI3K signaling, such as in PTEN mutant cancer cells. This study provides a novel mechanism of TAZ regulation and suggests a role of TAZ in modulating tissue growth and tumor development in response to PI3K signaling.
  Journal of Biological Chemistry 06/2012; 287(31):26245-53. · 4.77 Impact Factor
• Article: PP1 Cooperates with ASPP2 to Dephosphorylate and Activate TAZ

  Chen-Ying Liu, Xianbo Lv, Tingting Li, Yanping Xu, Xin Zhou, Shimin Zhao, Yue Xiong, Qun-Ying Lei, Kun-Liang Guan
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  ABSTRACT: The Hippo pathway regulates organ size by controlling both cell proliferation and apoptosis. TAZ functions as a transcriptional co-activator downstream of the Hippo pathway and has been implicated in human cancer development. A key step in the Hippo-TAZ pathway is phosphorylation of TAZ by LATS kinase, which leads to TAZ inhibition by both cytoplasmic retention and degradation. However, the mechanism of TAZ dephosphorylation and the responsible phosphatase are unknown. Here, we identified PP1 as a bona fide TAZ phosphatase. PP1A dephosphorylates TAZ at Ser-89 and Ser-311, promotes TAZ nuclear translocation, and stabilizes TAZ by disrupting the binding to the SCF E3 ubiquitin ligase. Furthermore, ASPP2 facilitates the interaction between TAZ and PP1 to promote TAZ dephosphorylation. As a result, PP1 and ASPP2 increase TAZ-dependent gene expression. This study demonstrates that PP1A and ASPP2 play a critical role in promoting TAZ function by antagonizing the LATS kinase through TAZ dephosphorylation.
  Journal of Biological Chemistry 02/2011; 286(7):5558-5566. · 4.77 Impact Factor
• Article: PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ.

  Chen-Ying Liu, Xianbo Lv, Tingting Li, Yanping Xu, Xin Zhou, Shimin Zhao, Yue Xiong, Qun-Ying Lei, Kun-Liang Guan
  [show abstract] [hide abstract]
  ABSTRACT: The Hippo pathway regulates organ size by controlling both cell proliferation and apoptosis. TAZ functions as a transcriptional co-activator downstream of the Hippo pathway and has been implicated in human cancer development. A key step in the Hippo-TAZ pathway is phosphorylation of TAZ by LATS kinase, which leads to TAZ inhibition by both cytoplasmic retention and degradation. However, the mechanism of TAZ dephosphorylation and the responsible phosphatase are unknown. Here, we identified PP1 as a bona fide TAZ phosphatase. PP1A dephosphorylates TAZ at Ser-89 and Ser-311, promotes TAZ nuclear translocation, and stabilizes TAZ by disrupting the binding to the SCF E3 ubiquitin ligase. Furthermore, ASPP2 facilitates the interaction between TAZ and PP1 to promote TAZ dephosphorylation. As a result, PP1 and ASPP2 increase TAZ-dependent gene expression. This study demonstrates that PP1A and ASPP2 play a critical role in promoting TAZ function by antagonizing the LATS kinase through TAZ dephosphorylation.
  Journal of Biological Chemistry 02/2011; 286(7):5558-66. · 4.77 Impact Factor