MOS IS DEGRADED BY THE 26S PROTEASOME IN A UBIQUITIN-DEPENDENT FASHION

Mos, the c-mos proto-oncogene product, is a key regulator of cell cycl e progression. Recently, rapid turnover of Mos in an early stage of me iotic maturation of Xenopus oocytes was found to be mediated by the ub iquitin pathway, but the protease responsible for its breakdown was no t identified. In the present study, we found that S-35-labeled Mos syn thesized in an in vitro transcription/translation system was degraded ATP- and time-dependently by the 26S proteasome, but not by the 20S pr oteasome, in the presence of a ubiquitin-ligation system. The 26S prot easome did not degrade a mutant Mos in which Ser3 was replaced by Asp3 that is metabolically stable in oocytes, indicating a similarity in t he proteolytic events in vivo to those observed in vitro in the presen t work. This is the first demonstration that the proteasome catalyzes the ATP-dependent degradation of a naturally occurring, short-lived on coprotein by the ubiquitin pathway. This finding suggests that the pro teasome may regulate the intracellular stability of various oncoprotei ns.