Current Location:home > Browse

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 Hits2222Downloads1221 Comment 0

2. chinaXiv:201605.01301 [pdf]

The Long Noncoding RNA IncTCF7 Promotes Self-Renewal of Human Liver Cancer Stem Cells through Activation of Wnt Signaling

Wang, Yanying; Du, Ying; Zhu, Pingping; Huang, Guanling; Yan, Xinlong; Ye, Buqing; Li, Chong; Xia, Pengyan; Zhang, Geng; Fan, Zusen; He, Lei; Huang, Guanling; Fan, Zusen; Luo, Jianjun; Tian, Yong; Chen, Runsheng
Subjects: Biology >> Biophysics

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer, and it is characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanisms underlying their self-renewal and maintenance are poorly understood. Here, using transcriptome microarray analysis, we identified a long noncoding RNA (IncRNA) termed IncTCF7 that is highly expressed in HCC tumors and liver CSCs. LncTCF7 is required for liver CSC self-renewal and tumor propagation. Mechanistically, IncTCF7 recruits the SWI/SNF complex to the promoter of TCF7 to regulate its expression, leading to activation of Wnt signaling. Our data suggest that IncTCF7-mediated Wnt signaling primes liver CSC self-renewal and tumor propagation. In sum, therefore, we have identified an IncRNA-based Wnt signaling regulatory circuit that promotes tumorigenic activity in liver cancer stem cells, highlighting the role that IncRNAs can play in tumor growth and propagation.

submitted time 2016-05-11 Hits1714Downloads1089 Comment 0

3. chinaXiv:201605.00717 [pdf]

Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity

Xia, Pengyan; Ye, Buqing; Wang, Shuo; Du, Ying; Xiong, Zhen; Fan, Zusen; Zhu, Xiaoxiao; Xiong, Zhen; Fan, Zusen; Tian, Yong; Tian, Yong;
Subjects: Biology >> Biophysics >> Immunology

Cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA during viral infection and catalyzes synthesis of the dinucleotide cGAMP, which activates the adaptor STING to initiate antiviral responses. Here we found that deficiency in the carboxypeptidase CCP5 or CCP6 led to susceptibility to DNA viruses. CCP5 and CCP6 were required for activation of the transcription factor IRF3 and interferons. Polyglutamylation of cGAS by the enzyme TTLL6 impeded its DNA-binding ability, whereas TTLL4-mediated monoglutamylation of cGAS blocked its synthase activity. Conversely, CCP6 removed the polyglutamylation of cGAS, whereas CCP5 hydrolyzed the monoglutamylation of cGAS, which together led to the activation of cGAS. Therefore, glutamylation and deglutamylation of cGAS tightly modulate immune responses to infection with DNA viruses.

submitted time 2016-05-05 Hits1893Downloads981 Comment 0

  [1 Pages/ 3 Totals]