Polyubiquitinated proteins in eukaryotes are directed to the proteasome for degradation. It is generally accepted that proteasome-mediated proteolysis depends strictly upon ubiquitination, as disruption of that process has been observed to halt proteolytic activity of the proteasome. Researchers at Harvard Medical School have made the striking observation that a non-ubiquitinated protein, if linked to the proteasome complex, will undergo efficient degradation. The invention provides methods for directed, conditional degradation of proteins, both in vitro and in vivo.