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.
Highlights
In year 2000, we and two other groups have independently discovered a candidate tumor suppressor, named WW domain-containing oxidoreductase [1-7; reviews]
Sex steroid hormones estrogen and androgen may interact with an N-S-Y-Kmotif in the shortchain alcohol dehydrogenase/reductase (SDR) domain that allows relocation of WWOX/WOX1 to the nucleus [3,7]
WWOX/WOX1 is known to increase the cytotoxic function of tumor necrosis factor (TNF) in killing cancer cells [1,2,3,7,8]
Summary
Subhan Dudekula1, Ming‐Hui Lee1, Li‐Jin Hsu2, Shean‐Jen Chen3, and Nan‐Shan Chang1,4 © 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
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