Degradation of Mos by the N-terminal proline (Pro2)-dependent ubiquitin pathway on fertilization of Xenopus eggs: possible significance of natural selection for Pro2 in Mos.
The c-mos proto-oncogene product (Mos), an essential component of the cytostatic factor responsible for meiotic arrest in vertebrate eggs, undergoes specific proteolysis soon after fertilization or activation of Xenopus eggs. To determine the degradation pathway of Mos on egg activation, 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 maturation, where Mos has been shown to be degraded by the 'second-codon rule'-based ubiquitin pathway. To test whether Mos degradation on egg activation is also mediated by the ubiquitin pathway, we attempted to identify and abrogate a specific ubiquitination site(s) in Mos. We show that the major ubiquitination site in Mos is a Lys34 residue and that replacement of this residue with a non-ubiquitinatable Arg residue markedly enhances the stability of Mos on egg activation. These results indicate that the degradation of Mos on egg activation or fertilization is mediated primarily by the N-terminal Pro2-dependent ubiquitin pathway, as in meiosis I of oocyte maturation. The N-terminal Pro2 residue of Mos appears to be naturally selected primarily for its degradation on fertilization, rather than that in meiosis I.
Nishizawa
M
M
Division of Molecular Genetics, Kurume University, Fukuoka, Japan.
Furuno
N
N
Okazaki
K
K
Tanaka
H
H
Ogawa
Y
Y
Sagata
N
N
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005306:Fertilization / Q000502:physiology*; D006801:Humans; D008540:Meiosis; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D017231:Proto-Oncogene Proteins c-mos / Q000235:genetics / Q000378:metabolism*; D012641:Selection, Genetic; D012694:Serine / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*; D014981:Xenopus
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014452:Ubiquitins; D012694:Serine; D011392:Proline; D017231:Proto-Oncogene Proteins c-mos