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10.1074/jbc.M115.655597

http://scihub22266oqcxt.onion/10.1074/jbc.M115.655597
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suck abstract from ncbi


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pmid26442585
      J+Biol+Chem 2015 ; 290 (47 ): 28200-28213
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  • A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor #MMPMID26442585
  • Wang Y ; Zheng Z ; Zhang J ; Wang Y ; Kong R ; Liu J ; Zhang Y ; Deng H ; Du X ; Ke Y
  • J Biol Chem 2015[Nov]; 290 (47 ): 28200-28213 PMID26442585 show ga
  • Retinoblastoma protein (RB) plays critical roles in tumor suppression and is degraded through the proteasomal pathway. However, E3 ubiquitin ligases responsible for proteasome-mediated degradation of RB are largely unknown. Here we characterize a novel RB E3 ubiquitin ligase (NRBE3) that binds RB and promotes RB degradation. NRBE3 contains an LXCXE motif and bound RB in vitro. NRBE3 interacted with RB in cells when proteasome activity was inhibited. NRBE3 promoted RB ubiquitination and degradation via the ubiquitin-proteasome pathway. Importantly, purified NRBE3 ubiquitinated recombinant RB in vitro, and a U-box was identified as essential for its E3 activity. Surprisingly, NRBE3 was transcriptionally activated by E2F1/DP1. Consequently, NRBE3 affected the cell cycle by promoting G1/S transition. Moreover, NRBE3 was up-regulated in breast cancer tissues. Taken together, we identified NRBE3 as a novel ubiquitin E3 ligase for RB that might play a role as a potential oncoprotein in human cancers.
  • |Amino Acid Sequence [MESH]
  • |Base Sequence [MESH]
  • |Breast Neoplasms/physiopathology [MESH]
  • |Cell Line, Tumor [MESH]
  • |DNA [MESH]
  • |E2F1 Transcription Factor/*physiology [MESH]
  • |Female [MESH]
  • |Gene Expression Regulation/*physiology [MESH]
  • |Humans [MESH]
  • |Molecular Sequence Data [MESH]
  • |Promoter Regions, Genetic [MESH]
  • |Proteolysis [MESH]
  • |Retinoblastoma Binding Proteins [MESH]
  • |Retinoblastoma Protein/*metabolism [MESH]
  • |Sequence Homology, Amino Acid [MESH]
  • |Transcription, Genetic/*physiology [MESH]
  • |Ubiquitin-Protein Ligases/chemistry/*physiology [MESH]


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