Dissection of c-MOS degron

AUTOR(ES)

Sheng, Jun

FONTE

Oxford University Press

RESUMO

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.

Documentos Relacionados

• Complete c-mos (rat) nucleotide sequence: presence of conserved domains in c-mos proteins.
• Mouse c-mos oncogene activation is prevented by upstream sequences.
• Human proto-oncogene c-mos maps to 8q11.
• Expression of c-mos RNA in germ cells of male and female mice.
• Identification of a negative regulatory element that inhibits c-mos transcription in somatic cells.