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Lysine 33 polyubiquitin chain formation by the HECT Ubiquitin E3 Ligase AREL1
Author(s) -
Ladda Emily Rose,
Spratt Donald
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09644
Subject(s) - ubiquitin , ubiquitin ligase , dna ligase , chemistry , lysine , microbiology and biotechnology , biochemistry , proteasome , biology , dna , amino acid , gene
Apoptosis Resistant E3 Ligase 1 (AREL1) is a member of the Homologous to E6AP Carboxyl Terminus (HECT) E3 ubiquitin ligase family. All HECT E3 ubiquitin ligases contain a conserved HECT domain that facilitate the covalent attachment of ubiquitin onto their intracellular substrates. Ubiquitylation is involved in numerous cell signaling pathways that can result in proteasomal degradation, DNA damage repair, and cell trafficking, among others. The biological function of AREL1 is to inhibit intrinsic apoptosis by ubiquitylation of pro‐apoptotic inhibitor of apoptosis (IAP) antagonist proteins, SMAC, ARTS, and HtrA2, for proteasomal degradation. Interestingly, previous studies have found that AREL1 is the only HECT E3 ubiquitin ligase identified to date that is capable of building polyubiquitin chains via lysine 33 linkages, and the biological role of this linkage remains unclear. Using circular dichroism (CD), in vitro ubiquitin activity assays, disulfide complex formation, and multidimensional heteronuclear NMR spectroscopy, we are currently deciphering the unique molecular mechanism used by AREL1 to build the lysine 33 poly‐ubiquitin chains. Support or Funding Information NIH NIGMS Maurine H. Milburn Fund Clark University Carlson School of Biochemistry and Chemistry