Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3

Xiaoli Wang, Roger A. Herr, Wei Jen Chua, Lonnie Lybarger, Emmanuel J H J Wiertz, Ted H. Hansen

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

The mechanism by which substrates for endoplasmic reticulum-associated degradation are retrotranslocated to the cytosol remains largely unknown, although ubiquitination is known to play a key role. The mouse γ-herpesvirus protein mK3 is a viral RING-CH-type E3 ligase that specifically targets nascent major histocompatibility complex I heavy chain (HC) for degradation, thus blocking the immune detection of virus-infected cells. To address the question of how HC is retrotranslocated and what role mK3 ligase plays in this action, we investigated ubiquitin conjugation sites on HC using mutagenesis and biochemistry approaches. In total, our data demonstrate that mK3-mediated ubiquitination can occur via serine, threonine, or lysine residues on the HC tail, each of which is sufficient to induce the rapid degradation of HC. Given that mK3 has numerous cellular and viral homologues, it will be of considerable interest to determine the pervasiveness of this novel mechanism of ubiquitination.

Original languageEnglish (US)
Pages (from-to)613-624
Number of pages12
JournalJournal of Cell Biology
Volume177
Issue number4
DOIs
StatePublished - May 21 2007

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Ubiquitin-Protein Ligases
Ubiquitination
Threonine
Serine
Lysine
Tail
Endoplasmic Reticulum-Associated Degradation
Herpesviridae
Ligases
Ubiquitin
Major Histocompatibility Complex
Mutagenesis
Biochemistry
Cytosol
Viruses
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3. / Wang, Xiaoli; Herr, Roger A.; Chua, Wei Jen; Lybarger, Lonnie; Wiertz, Emmanuel J H J; Hansen, Ted H.

In: Journal of Cell Biology, Vol. 177, No. 4, 21.05.2007, p. 613-624.

Research output: Contribution to journalArticle

Wang, Xiaoli ; Herr, Roger A. ; Chua, Wei Jen ; Lybarger, Lonnie ; Wiertz, Emmanuel J H J ; Hansen, Ted H. / Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3. In: Journal of Cell Biology. 2007 ; Vol. 177, No. 4. pp. 613-624.
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