BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5delta

Exp Cell Res. 2003 Aug 1;288(1):84-93. doi: 10.1016/s0014-4827(03)00187-3.


We previously identified BTBD1 and BTBD2 as novel topoisomerase I-interacting proteins that share 80% amino acid identity. Here we report the characterization of their subcellular localization. In a number of mouse and human cells, BTBD1 and BTBD2 (BTBD1/2) colocalized to punctate or elongated cytoplasmic bodies (< 5 microm long and several per cell) that were larger and more elongated in cancer cell lines than in fibroblasts and myoblasts. A search for potential colocalizing proteins identified TRIM family members that localize to morphologically similar cytoplasmic bodies, which were then tested for colocalization with BTBD1/2. TRIM5delta, expressed as a GFP fusion, colocalized with BTBD1/2 immunostaining and appeared to serve as a scaffold for the assembly of endogenous BTBD1/2 proteins. TRIM family members contain a RING domain, B-box(es), and coiled-coil regions, which have a characteristic order and spacing (RBCC domain). RING-dependent ubiquitin ligase activity and multimerization via the coiled-coil region may be defining properties of the RBCC/TRIM protein family. We found that TRIM5delta with a deleted coiled-coil region or a mutated RING domain failed to colocalize with BTBD1/2. Additionally, TRIM5delta ubiquitylated itself in a RING finger- and UbcH5B-dependent manner. BTBD1/2 each contain a PHR-similarity region, repeated twice on the putative ubiquitin ligases PAM, highwire and RPM-1, which also contain a RING and B-box. Thus, four protein modules found on each of these putative ubiquitin ligases, a RING, a B-box and two PHR repeats, are present on BTBD1/2 and TRIM5delta that are colocalized to cytoplasmic bodies.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antiviral Restriction Factors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cytoplasm / ultrastructure*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Mice
  • Mutation
  • Protein Structure, Tertiary
  • Protein Transport
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Tripartite Motif Proteins
  • Tumor Cells, Cultured
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases


  • Antiviral Restriction Factors
  • BTBD1 protein, human
  • BTBD2 protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • Transcription Factors
  • Tripartite Motif Proteins
  • Ubiquitin
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases