[新闻]新发现基因可能控制慢性感染，如HIV，肝炎和肺结核

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Title: ARIH2 is essential for embryogenesis, and its hematopoietic deficiency causes lethal activation of the immune system
Author: Lin, A. E.; Ebert, G.; Ow, Y. (...)
Source: Nat Immunol, 2013, 14(1): 27-33
Abstract:
  The E3 ligase ARIH2 has an unusual structure and mechanism of elongating ubiquitin chains. To understand its physiological role, we generated gene-targeted mice deficient in ARIH2. ARIH2 deficiency resulted in the embryonic death of C57BL/6 mice. On a mixed genetic background, the lethality was attenuated, with some mice surviving beyond weaning and then succumbing to an aggressive multiorgan inflammatory response. We found that in dendritic cells (DCs), ARIH2 caused degradation of the inhibitor IkappaBbeta in the nucleus, which abrogated its ability to sequester, protect and transcriptionally coactivate the transcription factor subunit p65 in the nucleus. Loss of ARIH2 caused dysregulated activation of the transcription factor NF-kappaB in DCs, which led to lethal activation of the immune system in ARIH2-sufficent mice reconstituted with ARIH2-deficient hematopoietic stem cells. Our data have therapeutic implications for targeting ARIH2 function.
http://www.nature.com/ni/journal/v14/n1/abs/ni.2478.html