Research

A novel acetylation cycle of the transcription co-activator Yes-associated protein that is downstream of the Hippo pathway is triggered in response to SN2 alkylating agents


Reference:

Hata, S., Hirayama, J., Kajiho, H., Nakagawa, K., Hata, Y., Katada, T., Furutani-seiki, M. and Nishina, H., 2012. A novel acetylation cycle of the transcription co-activator Yes-associated protein that is downstream of the Hippo pathway is triggered in response to SN2 alkylating agents. Journal of Biological Chemistry, 287, pp. 22089-22098.

Related documents:

This repository does not currently have the full-text of this item.
You may be able to access a copy if URLs are provided below. (Contact Author)

Official URL:

http://dx.doi.org/10.1074/jbc.M111.334714

Abstract

Yes-associated protein (YAP) is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes. Although cytoplasmic retention of YAP is known to be mediated by Hippo pathway-dependent phosphorylation, post-translational modifications that regulate YAP in the nucleus remain unclear. Here we report the discovery of a novel cycle of acetylation/deacetylation of nuclear YAP induced in response to SN2 alkylating agents. We show that after treatment of cells with the SN2 alkylating agent methyl methanesulfonate, YAP phosphorylation mediated by the Hippo pathway is markedly reduced, leading to nuclear translocation of YAP and its acetylation. This YAP acetylation occurs on specific and highly conserved C-terminal lysine residues and is mediated by the nuclear acetyltransferases CBP (CREB binding protein) and p300. Conversely, the nuclear deacetylase SIRT1 is responsible for YAP deacetylation. Intriguingly, we found that YAP acetylation is induced specifically by SN2 alkylating agents and not by other DNA-damaging stimuli. These results identify a novel YAP acetylation cycle that occurs in the nucleus downstream of the Hippo pathway. Intriguingly, our findings also indicate that YAP acetylation is involved in responses to a specific type of DNA damage.

Details

Item Type Articles
CreatorsHata, S., Hirayama, J., Kajiho, H., Nakagawa, K., Hata, Y., Katada, T., Furutani-seiki, M. and Nishina, H.
DOI10.1074/jbc.M111.334714
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code31142

Export

Actions (login required)

View Item