The transcription factor ATF2 elicits oncogenic activities in melanoma and tumor suppressor activities in nonmalignant skin cancer. Here, we identify that ATF2 tumor suppressor function is determined by its ability to localize at the mitochondria, where it alters membrane permeability following genotoxic stress. The ability of ATF2 to reach the mitochondria is determined by PKCε, which directs ATF2 nuclear localization. Genotoxic stress attenuates PKCε effect on ATF2; enables ATF2 nuclear export and localization at the mitochondria, where it perturbs the HK1-VDAC1 complex; increases mitochondrial permeability; and promotes apoptosis. Significantly, high levels of PKCε, as seen in melanoma cells, block ATF2 nuclear export and function at the mitochondria, thereby attenuating apoptosis following exposure to genotoxic stress. In melanoma tumor samples, high PKCε levels associate with poor prognosis. Overall, our findings provide the framework for understanding how subcellular localization enables ATF2 oncogenic or tumor suppressor functions.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
Total Visit :3,824,801
Total Download :1,608,537
Today View :126
Ajou University Medical Information & Media Center 164 Worldcup-ro Yeongtong-gu Suwon 16499 Korea / TEL : 031-219-5312 / FAX : 031-219-5314 Copyright (c) Ajou University Medical Information & Media Center All Rights Reserved. AJOU Open Repository는 국립중앙도서관 OAK 보급사업으로 구축되었습니다.