The intrinsically disordered N-terminal domain of thymidylate synthase targets the enzyme to the ubiquitin-independent proteasomal degradation pathway.

ABSTRACT: The ubiquitin-independent proteasomal degradation pathway is increasingly being recognized as important in regulation of protein turnover in eukaryotic cells. One substrate of this pathway is the pyrimidine biosynthetic enzyme thymidylate synthase (TS; EC 2.1.1.45), which catalyzes the reductive methylation of dUMP to form dTMP and is essential for DNA replication during cell growth and proliferation. Previous work from our laboratory showed that degradation of TS is ubiquitin-independent and mediated by an intrinsically disordered 27-residue region at the N-terminal end of the molecule. In the current study we show that this region, in cooperation with an alpha-helix formed by the next 15 residues, functions as a degron, i.e. it is capable of destabilizing a heterologous protein to which

SUBMITTER: Pena MM 

PROVIDER: S-EPMC2797230 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature