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Review
. 2011 Dec;1816(2):147-57.
doi: 10.1016/j.bbcan.2011.05.005. Epub 2011 Jun 6.

Ubiquitin-independent proteasomal degradation during oncogenic viral infections

Jiwon Hwang  1 , Laura Winkler, Robert F Kalejta
Affiliations
Review

Ubiquitin-independent proteasomal degradation during oncogenic viral infections

Jiwon Hwang et al. Biochim Biophys Acta. 2011 Dec.

Abstract

Most eukaryotic proteins destined for imminent destruction are first tagged with a chain of ubiquitin molecules and are subsequently dismantled by the proteasome. Ubiquitin-independent degradation of substrates by the proteasome, however, also occurs. The number of documented proteasome-dependent, ubiquitin-independent degradation events remains relatively small but continues to grow. Proteins involved in oncogenesis and tumor suppression make up the majority of the known cases for this type of protein destruction. Provocatively, viruses with confirmed or suspected oncogenic properties are also prominent participants in the pantheon of ubiquitin-independent proteasomal degradation events. In this review, we identify and describe examples of proteasome-dependent, ubiquitin-independent protein degradation that occur during tumor virus infections, speculate why this type of protein destruction may be preferred during oncogenesis, and argue that this uncommon type of protein turnover represents a prime target for antiviral and anticancer therapeutics.

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Figures

Figure 1
Figure 1. Models for ubiquitin-independent proteasomal degradation
A. Substrates undergoing proteasome-dependent, ubiquitin-independent degradation often associate with the 20S CP. This association can be direct and autonomous (i), direct but mediated by an accessory protein (ii), or indirect and mediated by an accessory protein (iii). B. Other proteasome-dependent ubiquitin-independent degradation substrates associate with proteasome activators. Mechanisms include substrate association with the 19S RP either independently (iv), with an accessory protein (v), or after conjugation with a ubiquitin-like protein (vi), as well as direct association with PA28γ (vii). Design adapted from reference 17.
Figure 2
Figure 2. Ubiquitin-independent proteasomal degradation events in vivo
The 20S CP alone or in association with various activators (19S RP, PA28αβ, PA200, PA28γ) mediates protein degradation (see text for details). Documented examples of ubiquitin-independent degradation events in uninfected cells (grey boxes) or in virus protein-expressing cells (yellow boxes) are displayed adjacent to the proteasomal components that mediate the event. Other proteasome-dependent, ubiquitin-independent degradation events in viral protein-expressing cells have not been ascribed to a specific proteasomal assemblage (white box). Design adapted from reference 17.
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