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1. chinaXiv:201605.01376 [pdf]

The Endoplasmic Reticulum Adaptor Protein ERAdP Initiates NK Cell Activation via the Ubc13-Mediated NF-kappa B Pathway

Chen, Jun; Hao, Lu; Li, Chong; Ye, Buqing; Du, Ying; Zhang, Honglian; Zhu, Pingping; Liu, Benyu; Yang, Liuliu; Fan, Zusen; Chen, Jun; Hao, Lu; Long, Bo; Long, Bo; Li, Peifeng; Tian, Yong
Subjects: Biology >> Biophysics >> Immunology

NK cells play a pivotal role in innate immune responses against pathogenic infections. However, the underlying mechanisms driving defined NK functions remain largely elusive. In this study, we identified a novel endoplasmic reticulum (ER) membrane protein, ER adaptor protein (ERAdP), which is constitutively expressed in human and mouse NK cells. ERAdP is expressed at low levels in peripheral NK cells of hepatitis B virus-associated hepatocellular carcinoma patients. We show that ERAdP initiates NK cell activation through the NF-kappa B pathway. Notably, ERAdP interacts with ubiquitin-conjugating enzyme 13 (Ubc13) to potentiate its charging activity. Thus, ERAdP augments Ubc13-mediated NF-kappa B essential modulator ubiquitination to trigger the Ubc13-mediated NF-kappa B pathway, leading to NK cell activation. Finally, ERAdP transgenic mice display hyperactivated NK cells that are more resistant to pathogenic infections. Therefore, understanding the mechanism of ERAdP-mediated NK cell activation will provide strategies for treatment of infectious diseases.

submitted time 2016-05-12 Hits2223Downloads1221 Comment 0

2. chinaXiv:201605.01338 [pdf]

ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells

Zhu, Pingping; Wang, Yanying; Huang, Guanling; Du, Ying; Zhang, Geng; Yan, Xinlong; Xia, Pengyan; Ye, Buqing; Wang, Shuo; Hao, Lu; Wu, Jiayi; Fan, Zusen; He, Lei; Huang, Guanling; Hao, Lu; Wu, Jiayi; Fan, Zusen
Subjects: Biology >> Biophysics

Liver cancer stem cells (CSCs) have been identified and shown to have self-renewal and differentiation properties; however, the biology of these hepatic CSCs remains largely unknown. Here, we analyzed transcriptome gene expression profiles of liver CSCs and non-CSCs from hepatocellular carcinoma (HCC) cells lines and found that the transcription factor (TF) ZIC2 is highly expressed in liver CSCs. ZIC2 was required for the self-renewal maintenance of liver CSCs, as ZIC2 depletion reduced sphere formation and xenograft tumor growth in mice. We determined that ZIC2 acts upstream of the TF OCT4 and that ZIC2 recruits the nuclear remodeling factor (NURF) complex to the OCT4 promoter, thereby initiating OCT4 activation. In HCC patients, expression levels of the NURF complex were consistent with clinical severity and prognosis. Moreover, ZIC2 and OCT4 levels positively correlated to the clinicopathological stages of HCC patients. Altogether, our results indicate that levels of ZIC2, OCT4, and the NURF complex can be detected and used for diagnosis and prognosis prediction of HCC patients. Moreover, these factors may be potential therapeutic targets for eradicating liver CSCs.

submitted time 2016-05-11 Hits2170Downloads1154 Comment 0

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