DEGRADATION OF MOS BY THE N-TERMINAL PROLINE (PRO(2))-DEPENDENT UBIQUITIN PATHWAY ON FERTILIZATION OF XENOPUS EGGS - POSSIBLE SIGNIFICANCE OF NATURAL-SELECTION FOR PRO(2) IN MOS

The c-mos proto-oncogene product (Mos), an essential component of the cytostatic factor responsible for meiotic arrest in vertebrate eggs, u ndergoes specific proteolysis soon after fertilization or activation o f Xenopus eggs. To determine the degradation pathway of Mos on egg act ivation, various Mos mutants were expressed in Xenopus eggs and their degradation on egg activation was examined. Mos degradation absolutely required its penultimate proline (Pro2) residue and dephosphorylation of the adjacent serine (Ser3) residue. These degradation signals were essentially the same as those of Mos in meiosis I of Xenopus oocyte m aturation, where Mos has been shown to be degraded by the 'second-codo n rule'-based ubiquitin pathway. To test whether Mos degradation on eg g activation is also mediated by the ubiquitin pathway, we attempted t o identify and abrogate a specific ubiquitination site(s) in Mos. We s how that the major ubiquitination site in Mos is a Lys34 residue and t hat replacement of this residue with a non-ubiquitinatable Arg residue markedly enhances the stability of Mos on egg activation. These resul ts indicate that the degradation of Mos on egg activation or fertiliza tion is mediated primarily by the N-terminal Pro2-dependent ubiquitin pathway, as in meiosis I of oocyte maturation. The N-terminal Pro2 res idue of Mos appears to be naturally selected primarily for its degrada tion on fertilization, rather than that in meiosis I.