STRESS RESISTANCE IN SACCHAROMYCES-CEREVISIAE IS STRONGLY CORRELATED WITH ASSEMBLY OF A NOVEL TYPE OF MULTIUBIQUITIN CHAIN

The covalent attachment of ubiquitin (Ub) to short-lived or damaged pr oteins is believed to be the signal that initiates their selective deg radation. In several cases, it has been shown that the proteolytic sig nal takes the form of a multi-Ub chain in which successive Ub molecule s are linked tandemly at lysine 48 (K-48). Here we show that Ub molecu les can be linked together in vivo at two other lysine positions, lysi ne 29 (K-29) and lysine 63 (K-63). The formation of these alternative linkages is strongly dependent on the presence of the stress-related U b conjugating enzymes UBC4 and UBC5. Furthermore, expression of Ub car rying a K-63 to arginine 63 substitution in a strain of Saccharomyces cerevisiae that is missing the poly-Ub gene, UBI4, fails to compensate for the stress defects associated with these cells. Taken together, t hese results suggest that the formation of multi-Ub chains involving K -63 linkages plays an important role in the yeast stress response. In broader terms, these results also suggest that Ub is a versatile signa l in which different Ub chain configurations are used for different fu nctions.