title: Immune regulator ABIN1 suppresses HIV-1 transcription by negatively regulating the ubiquitination of Tat.
abstract: A20-binding inhibitor of NF-κB activation (ABIN1), an important immune regulator, was previously shown to be involved in HIV-1 replication. However, the reported studies done with overexpressed ABIN1 provided controversial results.
  
  
  
  Here we identified ABIN1 as a suppressor of HIV-1 transcription since transient knockdown of ABIN1 led to increased HIV-1 replication both in transformed Jurkat T cell line and in primary human CD4+ T lymphocytes. Depletion of ABIN1 specifically enhanced the HIV-1 transcription from the integrated genome during viral life cycle, but not the earlier steps such as reverse transcription or integration. Immunoprecipitation assays revealed that ABIN1 specifically inhibits the proto-oncogene HDM2 catalyzed K63-linked polyubiquitination of Tat at Lys71, which is critical for the transactivation activity of Tat. The ubiquitin chain binding activity of ABIN1 carried by UBAN domain turned out to be essential for the inhibitory role of ABIN1. The results of immunofluorescence localization experiments suggested that ABIN1 may obstruct Tat ubiquitination by redistributing some of HDM2 from the nucleus to the cytoplasm.
  
  
  
  Our findings have revealed ABIN1 as intrinsic suppressor of HIV-1 mRNA transcription by regulating the ubiquitination of Tat.
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Shiyou
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Clinical Laboratory, General Hospital of the Yangtze River Shipping, Wuhan, 430010, People's Republic of China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Cheng
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, People's Republic of China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, People's Republic of China.
authors.forename: Shuliang
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, People's Republic of China. min.wang@whu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, People's Republic of China. guodeyin@mail.sysu.edu.cn.|School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, People's Republic of China. guodeyin@mail.sysu.edu.cn.|School of Basic Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, 510080, People's Republic of China. guodeyin@mail.sysu.edu.cn.
authors.forename: Deyin
authors.initials: D
authors.lastname: Guo
mesh_terms: D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D000090063:Proto-Oncogene Mas; D014158:Transcription, Genetic; D054875:Ubiquitination; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C117046:TNIP1 protein, human; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: ABIN1; HDM2; HIV-1; Tat; Transcription; Ubiquitination