Editors' ChoiceProtein Degradation

Regulatory Paradigm Revealed

STKE  12 Oct 2004:
Vol. 2004, Issue 254, pp. tw367
DOI: 10.1126/stke.2542004tw367

A well-established mechanism for the controlled degradation of proteins involves phosphorylation of the target protein, which marks the protein as a target for ubiquitin E3 ligases. Ubiquitination then leads to proteasomal degradation of the protein. Gao et al. show that controlled degradation of the transcription factor c-Jun is regulated not by Jun phosphorylation per se, but by the phosphorylation-dependent activation of the ubiquitin E3 ligase Itch. The c-Jun N-terminal kinase (JNK), which phosphorylates and activates Jun, also phosphorylates and activates Itch, which then mediates enhanced degradation of Jun. This feedback mechanism appears to attenuate the signaling pathway that leads to the production of T helper 2-type cytokines and may help to control T cell activation.

M. Gao, T. Labuda, Y. Xia, E. Gallagher, D. Fang, Y.-C. Liu, M. Karin, Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch. Science 306, 271-275 (2004). [Abstract] [Full Text]