Yu Zeng

Publications (3)17.31 Total impact

• Source

  Available from: PubMed Central

  Article: REGγ is associated with multiple oncogenic pathways in human cancers.

  Jing He, Long Cui, Yu Zeng, Guangqiang Wang, Ping Zhou, Yuanyuan Yang, Lei Ji, Yanyan Zhao, Jiwu Chen, Zhuo Wang, Tieliu Shi, Pei Zhang, Rui Chen, Xiaotao Li
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  ABSTRACT: Recent studies suggest a role of the proteasome activator, REGγ, in cancer progression. Since there are limited numbers of known REGγ targets, it is not known which cancers and pathways are associated with REGγ. REGγ protein expressions in four different cancers were investigated by immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO) database search, microarray platform validation, differential expressions of REGγ in corresponding cancers were statistically analyzed. Genes highly correlated with REGγ were defined based on Pearson's correlation coefficient. Functional links were estimated by Ingenuity Core analysis. Finally, validation was performed by RT-PCR analysis in established cancer cell lines and IHC in human colon cancer tissues Here, we demonstrate overexpression of REGγ in four different cancer types by micro-tissue array analysis. Using meta-analysis of publicly available microarray databases and biological studies, we verified elevated REGγ gene expression in the four types of cancers and identified genes significantly correlated with REGγ expression, including genes in p53, Myc pathways, and multiple other cancer-related pathways. The predicted correlations were largely consistent with quantitative RT-PCR analysis. This study provides us novel insights in REGγ gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REGγ in multiple cancer types and implicate REGγ as a putative cancer marker.
  BMC Cancer 02/2012; 12:75. · 3.01 Impact Factor
• Article: Regulation of REGγ cellular distribution and function by SUMO modification.

  Yan Wu, Lu Wang, Ping Zhou, Guangqiang Wang, Yu Zeng, Ying Wang, Jian Liu, Bianhong Zhang, Shuang Liu, Honglin Luo, Xiaotao Li
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  ABSTRACT: Discovery of emerging REGγ-regulated proteins has accentuated the REGγ-proteasome as an important pathway in multiple biological processes, including cell growth, cell cycle regulation, and apoptosis. However, little is known about the regulation of the REGγ-proteasome pathway. Here we demonstrate that REGγ can be SUMOylated in vitro and in vivo by SUMO-1, SUMO-2, and SUMO-3. The SUMO-E3 protein inhibitor of activated STAT (PIAS)1 physically associates with REGγ and promotes SUMOylation of REGγ. SUMOylation of REGγ was found to occur at multiple sites, including K6, K14, and K12. Mutation analysis indicated that these SUMO sites simultaneously contributed to the SUMOylation status of REGγ in cells. Posttranslational modification of REGγ by SUMO conjugation was revealed to mediate cytosolic translocation of REGγ and to cause increased stability of this proteasome activator. SUMOylation-deficient REGγ displayed attenuated ability to degrade p21(Waf//Cip1) due to reduced affinity of the REGγ SUMOylation-defective mutant for p21. Taken together, we report a previously unrecognized mechanism regulating the activity of the proteasome activator REGγ. This regulatory mechanism may enable REGγ to function as a more potent factor in protein degradation with a broader substrate spectrum.
  Cell Research 03/2011; 21(5):807-16. · 8.19 Impact Factor
• Article: REGgamma modulates p53 activity by regulating its cellular localization.

  Jian Liu, Guowu Yu, Yanyan Zhao, Dengpan Zhao, Ying Wang, Lu Wang, Jiang Liu, Lei Li, Yu Zeng, Yongyan Dang, Chuangui Wang, Guang Gao, Weiwen Long, David M Lonard, Shanlou Qiao, Ming-Jer Tsai, Bianhong Zhang, Honglin Luo, Xiaotao Li
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  ABSTRACT: The proteasome activator REGγ mediates a shortcut for the destruction of intact mammalian proteins. The biological roles of REGγ and the underlying mechanisms are not fully understood. Here we provide evidence that REGγ regulates cellular distribution of p53 by facilitating its multiple monoubiquitylation and subsequent nuclear export and degradation. We also show that inhibition of p53 tetramerization by REGγ might further enhance cytoplasmic relocation of p53 and reduce active p53 in the nucleus. Furthermore, multiple monoubiquitylation of p53 enhances its physical interaction with HDM2 and probably facilitates subsequent polyubiquitylation of p53, suggesting that monoubiquitylation can act as a signal for p53 degradation. Depletion of REGγ sensitizes cells to stress-induced apoptosis, validating its crucial role in the control of apoptosis, probably through regulation of p53 function. Using a mouse xenograft model, we show that REGγ knockdown results in a significant reduction of tumor growth, suggesting an important role for REGγ in tumor development. Our study therefore demonstrates that REGγ-mediated inactivation of p53 is one of the mechanisms involved in cancer progression.
  Journal of Cell Science 12/2010; 123(Pt 23):4076-84. · 6.11 Impact Factor