Kaposi's Sarcoma-associated Herpesvirus (KSHV) encodes a SUMO E3 ligase that is SIM-dependent and SUMO-2/3-specific

Pei Ching Chang, Yoshihiro Izumiya, Chun Yi Wu, Latricia D. Fitzgerald, Mel Campbell, Thomas J. Ellison, Kit S. Lam, Paul A. Luciw, Hsing Jien Kung

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Sumoylation has emerged as a major post-translational modification of cellular proteins, affecting a variety of cellular processes. Viruses have exploited the sumoylation pathway to advance their own replication by evolving several ways to perturb the host sumoylation apparatus. However, there has been no report of virally encoded enzymes directly involved in catalyzing the sumoylation reaction. Here, we report that the K-bZIP protein encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) is a SUMO E3 ligase with specificity toward SUMO2/3. K-bZIP is a nuclear factor that functions to modulate viral gene expression and to prolong the G1 phase, allowing viral transcription and translation to proceed at the early stage of infection. In addition to functioning as a transcriptional factor, we show that K-bZIP carries a SIM (SUMO-interacting motif), which specifically binds to SUMO-2/3 but not SUMO-1. K-bZIP catalyzes its own SUMO modification as well as that of its interacting partners such as the cellular tumor suppressor proteins p53 and Rb, both in vitro and in vivo. This reaction depends on an intact SIM. Sumoylation of p53 leads to its activation and K-bZIP is recruited to several p53 target chromatin sites in a SIM-dependent manner. In addition to the identification of a viral SUMO-2/3 E3 ligase, our results provide additional insights into the mechanisms whereby K-bZIP induces cell cycle arrest.

Original languageEnglish
Pages (from-to)5266-5273
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number8
DOIs
Publication statusPublished - Feb 19 2010
Externally publishedYes

Fingerprint

Sumoylation
Human Herpesvirus 8
Ubiquitin-Protein Ligases
Basic-Leucine Zipper Transcription Factors
Tumor Suppressor Protein p53
Transcription
Viruses
Gene expression
Chromatin
Chemical activation
Cells
Enzymes
Viral Genes
G1 Phase
Post Translational Protein Processing
Cell Cycle Checkpoints
Proteins
Gene Expression
Infection

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kaposi's Sarcoma-associated Herpesvirus (KSHV) encodes a SUMO E3 ligase that is SIM-dependent and SUMO-2/3-specific. / Chang, Pei Ching; Izumiya, Yoshihiro; Wu, Chun Yi; Fitzgerald, Latricia D.; Campbell, Mel; Ellison, Thomas J.; Lam, Kit S.; Luciw, Paul A.; Kung, Hsing Jien.

In: Journal of Biological Chemistry, Vol. 285, No. 8, 19.02.2010, p. 5266-5273.

Research output: Contribution to journalArticle

Chang, PC, Izumiya, Y, Wu, CY, Fitzgerald, LD, Campbell, M, Ellison, TJ, Lam, KS, Luciw, PA & Kung, HJ 2010, 'Kaposi's Sarcoma-associated Herpesvirus (KSHV) encodes a SUMO E3 ligase that is SIM-dependent and SUMO-2/3-specific', Journal of Biological Chemistry, vol. 285, no. 8, pp. 5266-5273. https://doi.org/10.1074/jbc.M109.088088
Chang, Pei Ching ; Izumiya, Yoshihiro ; Wu, Chun Yi ; Fitzgerald, Latricia D. ; Campbell, Mel ; Ellison, Thomas J. ; Lam, Kit S. ; Luciw, Paul A. ; Kung, Hsing Jien. / Kaposi's Sarcoma-associated Herpesvirus (KSHV) encodes a SUMO E3 ligase that is SIM-dependent and SUMO-2/3-specific. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 8. pp. 5266-5273.
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