Editors' ChoiceProtein Degradation

The N-end rule finds a physiological function

Science Signaling  17 Mar 2015:
Vol. 8, Issue 368, pp. ec65
DOI: 10.1126/scisignal.aab1180

The N-end–rule pathway for protein degradation is a canonical degradation pathway discovered in the 1980s. In recent years, studies have focused on finding novel variant pathways of N-end recognition. The “classical” pathway is blocked by N-terminal acetylation of the substrate. However, in yeast, N-terminal acetylation need not block degradation, because a second pathway can act on acetylated N termini. But is this alternate pathway a major player in the physiology of mammals? Park et al. now confirm the existence of the alternate pathway in mammalian cells. Most notably, patient-derived point mutations thought to confer hypertension in humans affect susceptibility to this pathway for the encoded protein substrate, RGS2.

S.-E. Park, J.-M. Kim, O.-H. Seok, H. Cho, B. Wadas, S.-Y. Kim, A. Varshavsky, C.-S. Hwang, Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway. Science 347, 1249–1252 (2015). [Abstract] [Full Text]