title: Dissection of c-MOS degron.
abstract: c-MOS, a MAP kinase kinase kinase, is a regulator of oocyte maturation. The concentration of c-MOS is controlled in part through its conditional degradation. Previous studies proposed the "second-codon rule", according to which the N-terminal proline (Pro) of c-MOS is a destabilizing residue that targets c-MOS for degradation. We analyzed the degradation signal (degron) of c-MOS in Xenopus oocytes, found it to be a portable degron, and demonstrated that, contrary to the model above, the N-terminal Pro residue of c-MOS is entirely dispensable for its degradation if Ser-2 (encoded Ser-3) of c-MOS is replaced by a small non-phosphorylatable residue such as Gly. The dependence of c-MOS degradation on N-terminal Pro is shown to be caused by a Pro-mediated downregulation of the net phosphorylation of Ser-2, a modification that halts c-MOS degradation in oocytes. Thus, the N-terminal Pro residue of c-MOS is not a recognition determinant for a ubiquitin ligase, in agreement with earlier evidence that Pro is a stabilizing residue in the N-end rule.
authors.affiliation: Division of Biology, 147-75, California Institute of Technology, 1200 East California Blvd, Pasadena, CA 91125, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Sheng
authors.forename: Akiko
authors.initials: A
authors.lastname: Kumagai
authors.forename: William G
authors.initials: WG
authors.lastname: Dunphy
authors.forename: Alexander
authors.initials: A
authors.lastname: Varshavsky
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D010450:Endopeptidases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016258:Genes, mos; D008025:Ligases / Q000378:metabolism; D051379:Mice; D008845:Microinjections; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry; D011374:Progesterone; D011392:Proline / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D017231:Proto-Oncogene Proteins c-mos / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism; D013045:Species Specificity; D014982:Xenopus laevis
chemical_list: D011993:Recombinant Fusion Proteins; D010768:Phosphoserine; D011374:Progesterone; D011392:Proline; D017231:Proto-Oncogene Proteins c-mos; D010450:Endopeptidases; D008025:Ligases