title: NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes.
abstract: BRCC36-deubiquitinating enzyme (DUB) forms two different complexes through interactions with two different adaptor proteins Abraxas and ABRO1 in cells. Abraxas mainly localizes in the nucleus, mediating the interaction of BRCC36 with BRCA1. ABRO1 is mainly localized in the cytoplasm. Because it lacks the BRCA1-interacting motif, the ABRO1 complex does not interact with BRCA1. Both BRCC36-containing complexes contain common components including BRE and NBA1/MERIT40. Here, we found that the two complexes are assembled in a similar manner and NBA1 and BRE interaction is critical for maintaining the integrity of both of the complexes. Knockdown of NBA1 or BRE leads to decreased levels of components of the two BRCC36-containing complexes. We provided evidence that NBA1 interacts with BRE through a C-terminal conserved motif of the NBA1 protein and a C-terminal UEV domain of the BRE protein. Furthermore, the NBA1-BRE interaction is required for cellular resistance to ionizing irradiation and NBA1's role in recruiting BRCA1 to DNA damage sites. Together, these studies reveal critical interactions required for the formation and function of BRCC36-containing DUB complexes.
authors.affiliation: Department of Genetics, The University of Texas M D Anderson Cancer Center, University of Texas Graduate School of Biomedical Sciences, Houston, Texas 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Andy
authors.initials: A
authors.lastname: Castillo
authors.forename: Michael
authors.initials: M
authors.lastname: Huang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D003593:Cytoplasm / Q000201:enzymology* / Q000235:genetics; D004249:DNA Damage / Q000502:physiology / Q000528:radiation effects; D000072017:Deubiquitinating Enzymes; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005720:Gamma Rays / Q000009:adverse effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: C520310:ABRAXAS1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C540398:BABAM1 protein, human; C091514:BABAM2 protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D010450:Endopeptidases; C518017:BRCC3 protein, human; D000072017:Deubiquitinating Enzymes