N-Terminal Protein Acetylation and Apoptosis Are Functionally Linked

A new study shows that proteins called IAPs, are inhibited by a specific chemical modification, and reveals that they play a wider role in protein quality control than previously assumed. Researchers from the Ludwig-Maximilians University in Munich have shown that N-terminal acetylation shields certain proteins from degradation, and inhibits apoptosis. Their work was published in Science Advances. 

While the acronym refers to the function of IAPs as inhibitors of apoptosis, the new study suggests that they actually have a more general role in protein quality control. The work demonstrates for the first time that two fundamental cellular processes—N-terminal protein acetylation and programmed cell death—are functionally linked. 

"In our experiments, we observed that a protein which is not involved in the control of apoptosis also binds exclusively to IAPs in its non-acetylated form," lead researcher Tanja Bange explains. "This prompted us to explore the role of acetylation in the binding of proteins to IAPs in general."

In experiments on cultured cells, Bange and her colleagues were able to show that, as a general rule, IAPs indeed bind to proteins whose N-termini are unacetylated. It is also known that IAPs are able to induce their own destruction as well as the degradation of their binding partners. The authors therefore assume that IAPs have a hitherto unrecognized and general function in the quality control of newly synthesized proteins. 

"N-terminal acetylation protects proteins from degradation," says Bange. "If its N-terminus is not 'capped' in this way, a protein is recognized as defective by IAPs and destroyed. Conversely, if proteins that lack the modification accumulate in sufficient numbers, apoptosis is triggered." According to the authors, inhibiting N-terminal acetylation pathways might provide a means of activating IAP function and sensitizing tumor cells to apoptosis.