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Research Perspective|Volume 2, Issue 12|pp 1023—1029

Zfra is a small wizard in the mitochondrial apoptosis

Subhan Dudekula1, Ming-Hui Lee1, Li-Jin Hsu2, Shean-Jen Chen3, Nan-Shan Chang1,4
  • 1Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC
  • 2Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan, Taiwan, ROC
  • 3Department of Engineering Science, National Cheng Kung University Medical College, Tainan, Taiwan, ROC
  • 4Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA
Received: December 11, 2010Accepted: December 26, 2010Published: December 27, 2010
https://doi.org/10.18632/aging.100263

Copyright: © 2010 Dudekula et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Zfra (zinc finger-like protein that regulates apoptosis) is a naturally occurring short peptide consisting of 31 amino acids, which regulates tumor necrosis factor (TNF)-mediated cell death by interacting with receptor adaptor protein TRADD (TNF receptorassociated death domain protein) and downstream JNK (c-Jun N-terminal kinase), NF-κB (Nuclear factor kappa B) and WWOX/WOX1 (WW domain-containing oxidoreductase). Cytochrome c release is generally considered as a pivotal step in apoptosis. Remarkably, overexpressed Zfra induces apoptosis via the mitochondrial pathway, which involves suppression of Bcl-2 and Bcl-xL expression (without causing cytochrome c release), counteracting the apoptotic function of tumor suppressor p53 and WWOX, and dissipation of mitochondrial membrane potential for ultimately leading to cell death. Control of cellular aging and apoptosis by Zfra, p53 and WWOX is discussed.