Ετικέτες

Τετάρτη 16 Αυγούστου 2017

The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity

Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R. Billiar, Michael T. Lotze, Herbert J. Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis. These findings reveal a direct molecular link between TP53 and DPP4 in the control of lipid metabolism and may provide a precision medicine strategy for the treatment of colorectal cancer by induction of ferroptosis.

Graphical abstract

image

Teaser

Xie et al. find that TP53 antagonizes ferroptosis in colorectal cancer (CRC) cells by favoring the localization of DPP4 toward a nuclear, enzymatically inactive pool. This pathway is different from the previously identified function of TP53 as a positive regulator of ferroptosis in non-CRC cells.


http://ift.tt/2vKn636

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου

Αναζήτηση αυτού του ιστολογίου