The ubiquitin-proteasome system is responsible for degradation of most of the cellular proteins, a process that is crucial for maintaining normal life course of the cell. Nevertheless, not all of the proteins degraded by the proteasome are ubiquitinated.

The most notable example is Ornithine Decarboxylase, ODC, the first and rate limiting enzyme in the polyamine biosynthesis pathway.

The degradation of ODC provides an alternative mechanism for targeting to the proteasome. ODC degradation by the proteasome is greatly stimulated by a polyamine-induced protein, termed Antizyme (Az), in a ubiquitin-independent manner.

ODC is active only as a homodimer. The heterodimerization of Az and ODC inactivates ODC as an intermediate step in the process of targeting it to degradation by the proteasome.

While ubiquitin recognition elements within the proteasome were extensively studied, the recognition element for the ODC and Az complex is still unknown.

The main goal of ourresearch is to shed light on two main aspects of this recognition process:

1) Identifying ODC recognition elements intrinsic or extrinsic to the proteasome.

2) Further characterization of the degradation signals within ODC and Az, which lead to ODC degradation.

In order to address these questions we use methods such as co-immunoprecipitatation, followed by 2D LCMS/MS, and different manipulations of the proteins.

We have also obtained yeast mutant strains, with deletions in proteasomal and non-proteasomal ubiquitin recognition elements, in order to investigate yeast ODC recognition and degradation by the yeast proteasome.