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キーワード:
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要旨:
Polyubiquitin chains linked via lysine (K) 63 play an important role in
endocytosis and membrane trafficking. Their primary source is the
ubiquitin protein ligase (E3) Rsp5/NEDD4, which acts as a key regulator
of membrane protein sorting. The heterodimeric ubiquitin-conjugating
enzyme (E2), Ubc13-Mms2, catalyses K63-specific polyubiquitylation in
genome maintenance and inflammatory signalling. In budding yeast, the
only E3 proteins known to cooperate with Ubc13-Mms2 so far is a nuclear
RING finger protein, Rad5, involved in the replication of damaged DNA.
Here, we report a contribution of Ubc13-Mms2 to the sorting of membrane
proteins to the yeast vacuole via the multivesicular body (MVB) pathway.
In this context, Ubc13-Mms2 cooperates with Pib1, a FYVE-RING finger
protein associated with internal membranes. Moreover, we identified a
family of membrane-associated FYVE(type)-RING finger proteins as cognate
E3 proteins for Ubc13-Mms2 in several species, and genetic analysis
indicates that the contribution of Ubc13-Mms2 to membrane trafficking in
budding yeast goes beyond its cooperation with Pib1. Thus, our results
widely implicate Ubc13-Mms2 as an Rsp5-independent source of K63-linked
polyubiquitin chains in the regulation of membrane protein sorting.
This article has an associated First Person interview with the first
author of the paper.
