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10.18632/oncotarget.13268 http://scihub22266oqcxt.onion/10.18632/oncotarget.13268 C5386674!5386674 !27845895     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27845895 &cmd=llinks): Failed to open stream: HTTP request failed! 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Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed |pdf=|usr=}}{{27845895 }} gab.com Text Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=27845895 #FOAvip Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-?), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-? binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. Twit Text FOAVip Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=27845895 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27845895 #FOAvip English Wikipedia <ref>{{Cite pmid|27845895 }}</ref> Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed #MMPMID27845895 Hsu LJ ; Hong Q ; Chen ST ; Kuo HL ; Schultz L ; Heath J ; Lin SR ; Lee MH ; Li DZ ; Li ZL ; Cheng HC ; Armand G ; Chang NS Oncotarget 2017[Mar]; 8 (12 ): 19137-19155 PMID27845895 show ga Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-?), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-? binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. |Animals [MESH] |Cell Death/*physiology [MESH] |Cell Line, Tumor [MESH] |Disease Models, Animal [MESH] |Fluorescence Resonance Energy Transfer [MESH] |Humans [MESH] |Hyaluronic Acid/*metabolism [MESH] |Immunoprecipitation [MESH] |Microscopy, Fluorescence [MESH] |Microscopy, Immunoelectron [MESH] |Neoplasms/metabolism/*pathology [MESH] |Oxidoreductases/*metabolism [MESH] |Rats [MESH] |Signal Transduction/*physiology [MESH] |Smad4 Protein/*metabolism [MESH] |Tumor Suppressor Proteins/*metabolism [MESH] |Two-Hybrid System Techniques [MESH]Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling c(epmc).pdf DeepDyve Pubget Overpricing