Zfra affects TNF-mediated cell death by interacting with death domain protein TRADD and negatively regulates the activation of NF-κB, JNK1, p53 and WOX1 during stress response

Abstract

Background: Zfra is a 31-amino-acid zinc finger-like protein, which is known to regulate cell death by tumor necrosis factor (TNF) and overexpressed TNF receptor-or Fas-associated death domain proteins (TRADD and FADD). In addition, Zfra undergoes self-association and interacts with c-Jun N-terminal kinase 1 (JNK1) in response to stress stimuli. To further delineate the functional properties of Zfra, here we investigated Zfra regulation of the activation of p53, WOX1 (WWOX or FOR), NF-κB, and JNK1 under apoptotic stress.

Regulation of cell signaling and apoptosis by tumor suppressor WWOX

“…55 Zfra is a 31-amino-acid protein that belongs to the C2H2 zinc-finger protein family. 56 Zfra is ubiquitously expressed in many organs and tissues, including the brain, heart, intestine, liver, lung, spleen, and testis.…”

WW Domain-Containing Oxidoreductase is a Potential Receptor for Sex Steroid Hormones

“…It is documented that there is a relative high percentage of loss of heterozygosity (LOH) from 30 to 50% in human WWOX gene in many types of cancer cells Smith et al, 2007;Del Mare et al, 2009;Chang et al, 2010). The WWOX/WOX1 protein is composed of a nuclear localization sequence (NLS), two Nterminal WW domains (containing conserved tryptophan residues), a C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, and probably a functional C-terminal tail named D3 (Hong et al, 2007;Hsu et al, 2008;Lin et al, 2011) (Figure 1). The putative tertiary structures of the first WW domain and the C-terminal SDR domain are shown.…”

“…The activated WWOX/WOX1 interacts with a large spectrum of proteins without possessing a PPXY motif(s), including proteins in the stress signaling and apoptotic response, as well as transcription factors Del Mare et al, 2009). These proteins are p53 (Lo et al, 2008;Chang et al, 2001Chang et al, , 2003aChang et al, , 2005aChang et al, , 2005bLai et al, 2005), JNK1 (Lo et al, 2008;Chang et al, 2003a), MDM2 (Chang et al, 2005a), Zfra (Hong et al, 2007;Hsu et al, 2008), and Hyal-2 ). The C-terminal SDR domain in WOX1/WWOX has been shown to bind Tau, a microtubulebinding protein involved in neurodegeneration (Sze et al, 2004).…”

Zfra induction of memory anticancer response via a novel immune cell

“…[1][2][3][4] Zfra participates in the tumor necrosis factor (TNF)-mediated apoptosis. [1][2][3][4] Zfra affects TNF signaling via interacting with TNF receptor adaptor proteins such as TRADD, FADD, and RIP.…”

“…[1][2][3][4] Zfra participates in the tumor necrosis factor (TNF)-mediated apoptosis. [1][2][3][4] Zfra affects TNF signaling via interacting with TNF receptor adaptor proteins such as TRADD, FADD, and RIP. [1][2][3][4] In addition, Zfra negatively controls the function of nuclear factor NF-kB, cJun N-terminal kinase 1 (JNK1), and tumor suppressors p53 and WW domain-containing oxidoreductase (WWOX, FOR, or WOX1).…”