Tension release by N-terminal acetylation

First published on UiB.no June 2, 2015.

Hypertension or high blood pressure is a major health problem that can result in cardiovascular diseases including hypertensive crisis and stroke. A recent paper in Science by Hwang and Varshavsky shows that the molecular signaling underlying regulation of blood pressure involves N-terminal acetylation of specific proteins and their consecutive degradation by the N-end rule pathway.

Taking the N-end rule to the next level.  A recent study links N-terminal acetylation and N-end rule degradation to blood pressure regulation. N-terminal mutants of Rgs2 (a key G-protein regulator) are found in patients with hypertension. These are differentially processed by N-terminal acetyltransferases (NATs) and the two branches of the N-end rule pathway. This leads to an imbalance in the signaling governing blood pressure. Refer to original potlight in TiBS for details. Copyright: Henriette Aksnes

Taking the N-end rule to the next level. A recent study links N-terminal acetylation and N-end rule degradation to blood pressure regulation. N-terminal mutants of Rgs2 (a key G-protein regulator) are found in patients with hypertension. These are differentially processed by N-terminal acetyltransferases (NATs) and the two branches of the N-end rule pathway. This leads to an imbalance in the signaling governing blood pressure. Refer to original potlight in TiBS for details. Copyright: Henriette Aksnes

Hypertension or high blood pressure is a major health problem that can result in cardiovascular diseases including hypertensive crisis and stroke. A recent paper in Science by Hwang and Varshavsky shows that the molecular signaling underlying regulation of blood pressure involves N-terminal acetylation of specific proteins and their consecutive degradation by the N-end rule pathway.

N-terminal acetylation is a modification that happens to about 80% of the cell’s proteins. For some N-terminally acetylated proteins, the modification is associated with a shorter molecular lifespan (half-life). However, we still know little about how such molecular effects of N-terminal acetylation are connected to physiological functioning. In a Spotlight article in Trends in Biochemical Sciences (TiBS), Aksnes and colleagues in the NAT group describe this recently revealed connection to blood pressure pathology to provide a new physiological understanding of the N-end rule pathway and N-terminal acetylation.


Research article

Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway

Park SE, Kim JM, Seok OH, Cho H, Wadas B, Kim SY, Varshavsky A, Hwang CS

Science. 2015 Mar 13;347(6227):1249-1252. .

Spotlight

(Hyper)tension release by N-terminal acetylation

Aksnes H, Drazic A, Arnesen T

Trends Biochem Sci. 2015 Aug;40(8):422-4.