Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5

Felipe Diaz-Griffero, Xing Li, Hassan Javanbakht, Byeongwoon Song, Sohanya Welikala, Matthew Stremlau, Joseph Sodroski

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

TRIM5α and TRIMCyp are retroviral restriction factors that, like other members of the tripartite motif (TRIM) family, contain RING, B-box 2 and coiled-coil domains. We found that both proteins are rapidly turned over, with half-lives of 50-60 min. Polyubiquitylation and rapid degradation of TRIM5α depended upon intact RING and B-box 2 domains. A chimera consisting of monkey TRIM5α with a RING domain of human TRIM21 exhibited a half-life of 210 min, yet potently restricted human immunodeficiency virus; therefore, rapid turnover of TRIM5α is not required for its antiretroviral activity. TRIM5α forms cytoplasmic bodies that contain other polyubiquitylated proteins, heat shock proteins and dynein, and thus resemble aggresome precursors. Consistent with this interpretation, proteasomal inhibitors triggered the formation of TRIM5αrh-containing aggresomes in a microtubule-dependent manner. Thus, TRIM5α levels in the cell are maintained by continuous synthesis and rapid proteasome-mediated degradation, imbalances in which result in the formation of pre-aggresomal cytoplasmic bodies.

Original languageEnglish (US)
Pages (from-to)300-315
Number of pages16
JournalVirology
Volume349
Issue number2
DOIs
StatePublished - Jun 5 2006
Externally publishedYes

Fingerprint

Dyneins
Proteasome Endopeptidase Complex
Heat-Shock Proteins
Microtubules
Haplorhini
Half-Life
Proteins
HIV

Keywords

  • Aggresome
  • Cytoplasmic body
  • Human immunodeficiency virus
  • Proteasome
  • RBCC
  • Restriction factor
  • TRIM5
  • TRIMCyp
  • Tripartite motif
  • Ubiquitin

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Diaz-Griffero, F., Li, X., Javanbakht, H., Song, B., Welikala, S., Stremlau, M., & Sodroski, J. (2006). Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5. Virology, 349(2), 300-315. https://doi.org/10.1016/j.virol.2005.12.040

Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5. / Diaz-Griffero, Felipe; Li, Xing; Javanbakht, Hassan; Song, Byeongwoon; Welikala, Sohanya; Stremlau, Matthew; Sodroski, Joseph.

In: Virology, Vol. 349, No. 2, 05.06.2006, p. 300-315.

Research output: Contribution to journalArticle

Diaz-Griffero, F, Li, X, Javanbakht, H, Song, B, Welikala, S, Stremlau, M & Sodroski, J 2006, 'Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5', Virology, vol. 349, no. 2, pp. 300-315. https://doi.org/10.1016/j.virol.2005.12.040
Diaz-Griffero, Felipe ; Li, Xing ; Javanbakht, Hassan ; Song, Byeongwoon ; Welikala, Sohanya ; Stremlau, Matthew ; Sodroski, Joseph. / Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5. In: Virology. 2006 ; Vol. 349, No. 2. pp. 300-315.
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