367 416

Cited 48 times in

PKCε promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria

Authors
Lau, E; Kluger, H; Varsano, T; Lee, K; Scheffler, I; Rimm, DL; Ideker, T; Ronai, ZA
Citation
Cell, 148(3):543-555, 2012
Journal Title
Cell
ISSN
0092-86741097-4172
Abstract
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.
MeSH terms
Activating Transcription Factor 2/*metabolism*ApoptosisCell LineCell Line, TumorCell Nucleus/metabolismCytosol/metabolismDNA DamageFibroblasts/metabolismHexokinase/metabolismHumansMelanoma/*metabolismMitochondria/*metabolismPrognosisProtein Kinase C-epsilon/*metabolismProtein TransportVoltage-Dependent Anion Channel 1/metabolism
DOI
10.1016/j.cell.2012.01.016
PMID
22304920
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Medical Informatics
AJOU Authors
이, 기영
Full Text Link
Files in This Item:
22304920.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse