Premium
Dissection of c‐MOS degron
Author(s) -
Sheng Jun,
Kumagai Akiko,
Dunphy William G.,
Varshavsky Alexander
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf626
Subject(s) - library science , archaeology , environmental ethics , history , philosophy , computer science
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.