Abstract LB-067: Critical role of Mieap, a p53-inducible protein, in intestinal tumor suppression
Authors: Nakamura Yasuyuki , Tsuneki Masayuki , Kinjyo Takashi , Kitamura Noriaki , Arakawa Hirofumi 
Published: August 2015

Abstract
Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria via MALM (Mieap-induced Accumulation of Lysosome-like organelles within Mitochondria) or MIV (Mieap-Induced Vacuole), respectively (1,2). Two mitochondrial outer membrane proteins, BNIP3 and NIX are essential mediators of MALM (3). 14-3-3gamma mediates the degradation of oxidized mitochondrial proteins in the MALM function (4). The Mieap-regulated mitochondrial quality control pathway was inactivated in almost 80% of colorectal cancer patients (5).
Here, we report that Mieap plays a critical role in mouse intestinal tumor suppression. To investigate a role of Mieap in intestinal tumorigenesis, we generated the Mieap-deficient ApcMIN/+ mice. The ApcMIN/+ mice with the Mieap+/− and Mieap−/− genetic background revealed the remarkable shortening of the lifetime, compared to ApcMIN/+ mice. Mieap deficiency caused the increased number and size of the intestinal tumors in ApcMIN/+ mice. In addition, the tumors in the Mieap-deficient ApcMIN/+ mice showed more advanced grade of malignancy and often became cancerous. The mitochondria in the intestine and tumor of the Mieap-deficient ApcMIN/+ mice were morphologically unhealthy and generated high level of reactive oxygen species. These results suggest that Mieap plays a critical role in intestinal tumor suppression through mitochondrial quality control and prevention of mitochondrial oxidative stress. The Mieap-regulated mitochondrial quality control is a critical function for p53 tumor suppressor.
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Citation Format: Yasuyuki Nakamura, Masayuki Tsuneki, Takashi Kinjyo, Noriaki Kitamura, Hirofumi Arakawa. Critical role of Mieap, a p53-inducible protein, in intestinal tumor suppression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-067. doi:10.1158/1538-7445.AM2015-LB-067