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test3

testone

bionlp-st-ge-2016-test-tees

bionlp-st-ge-2016-spacy-parsed

bionlp-st-ge-2016-test-ihmc

DLUT931

BioNLP16_Messiy

BioNLP16_DUT

bionlp-st-ge-2016-uniprot

bionlp-st-ge-2016-test-proteins

bionlp-st-ge-2016-coref

{"project":"bionlp-st-ge-2016-coref","denotations":[{"id":"T12884","span":{"begin":1831,"end":1835},"obj":"Anaphor"},{"id":"T12883","span":{"begin":1732,"end":1737},"obj":"Antecedent"},{"id":"T12882","span":{"begin":1721,"end":1726},"obj":"Antecedent"},{"id":"T12881","span":{"begin":1714,"end":1719},"obj":"Antecedent"},{"id":"T12880","span":{"begin":1803,"end":1817},"obj":"Anaphor"},{"id":"T12879","span":{"begin":1655,"end":1660},"obj":"Antecedent"},{"id":"T12878","span":{"begin":1768,"end":1779},"obj":"Anaphor"},{"id":"T3968","span":{"begin":4039,"end":4048},"obj":"Antecedent"},{"id":"T3967","span":{"begin":4095,"end":4100},"obj":"Anaphor"},{"id":"T3966","span":{"begin":3467,"end":3472},"obj":"Antecedent"},{"id":"T3965","span":{"begin":3458,"end":3461},"obj":"Antecedent"},{"id":"T3964","span":{"begin":3452,"end":3456},"obj":"Antecedent"},{"id":"T3963","span":{"begin":3483,"end":3488},"obj":"Anaphor"}],"relations":[{"id":"R2744","pred":"boundBy","subj":"T3963","obj":"T3964"},{"id":"R2745","pred":"boundBy","subj":"T3963","obj":"T3965"},{"id":"R2746","pred":"boundBy","subj":"T3963","obj":"T3966"},{"id":"R2747","pred":"boundBy","subj":"T3967","obj":"T3968"},{"id":"R8920","pred":"boundBy","subj":"T12878","obj":"T12879"},{"id":"R8921","pred":"boundBy","subj":"T12880","obj":"T12881"},{"id":"R8922","pred":"boundBy","subj":"T12880","obj":"T12882"},{"id":"R8923","pred":"boundBy","subj":"T12880","obj":"T12883"},{"id":"R8924","pred":"boundBy","subj":"T12884","obj":"T12881"},{"id":"R8925","pred":"boundBy","subj":"T12884","obj":"T12882"},{"id":"R8926","pred":"boundBy","subj":"T12884","obj":"T12883"}],"namespaces":[{"prefix":"_base","uri":"https://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"WW Domain-Containing Oxidoreductase WWOX\nRecently, tumor suppressors p53 and WWOX were shown to regulate the apoptosis of glioblastoma cells (Chiang et al., 2012). WW domain-containing oxidoreductase, known as WWOX, FOR, or WOX1, is encoded by human or mouse WWOX/Wwox gene. This gene is located in chromosome 16q23.3–24.1, an area known as the common fragile site FRA16D. The full-length WWOX protein is composed of two N-terminal WW domains, a C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, and a proapoptotic C-terminal tail D3 (Chang et al., 2001, 2007, 2010; Aqeilan et al., 2004, 2007; Hong et al., 2007; Salah et al., 2012) (Figure 1). WWOX may act as an alternative receptor for sex steroid hormones, since its SDR domain possesses an NSYK motif capable of interacting with androgen and estrogen (Chang et al., 2005a; Su et al., 2012).\nFigure 1 Schematic diagrams of WWOX structure and its role in signaling. WWOX contains two N-terminal WW domains, a C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, and a D3 region. A nuclear localization signal (NLS) is in between the WW domains (Chang et al., 2003, 2007; Del Mare et al., 2011; Salah et al., 2012; Su et al., 2012; reviews). The SDR domain possesses a mitochondria-binding region. There are two conserved tyrosine phosphorylation sites, Tyr33 and Tyr287. Other phosphorylation sites predicted by NetPhos 2.0 Server are Tyr6, Thr12, Ser14, Tyr61, Tyr293, and Thr3B3, respectively. Upon stress stimulation, WWOX is phosphorylated in Tyr33 and binds p53. The WWOX/p53 complex then translocates to mitochondria or nucleus to induce apoptosis. WWOX also binds PPxY motif-containing transcription factors, such as RUNX2, c-Jun, and ERBB4, via its first WW domain, and the binding blocks the activity of these proteins by retaining them in the cytoplasm. WWOX binds Tau via its SDR domain. WWOX participates in the Wnt/β-catenin signal pathway by binding Dvl and inhibiting its nuclear import. Phorbol ester stimulates the dissociation of MEK/WWOX complex in Jurkat T cell, and the released WWOX translocates to the mitochondria for causing cell death. WWOX is recruited to the membrane area by association with Hyal-2 and phospho-Ezrin. Hyal-2 is an alternative receptor for TGF-β1. In response to TGF-β1, WWOX binds Hyal-2 and forms a complex, followed by relocating to the nucleus and enhancing the SMAD-driven promoter activity. Ack1, activated Cdc42-associated kinase 1; Hyal-2, hyaluronoglucosaminidase 2; CKI, casein kinase; GSK, glycogen synthase kinase; PKA, protein kinase A. Expression of WWOX is either altered or lost from epigenetic modification in multiple malignant cancers, such as non-small cell lung carcinoma (Donati et al., 2007), hematopoietic malignancies (Ishii and Furukawa, 2004), gastric carcinoma (Aqeilan et al., 2004), pancreatic carcinoma (Kuroki et al., 2004), breast carcinoma (Guler et al., 2004; Aqeilan et al., 2007), and glioblastoma multiforme (Kosla et al., 2011). Restoration of WWOX gene prevents the growth of lung cancer (Fabbri et al., 2005), pancreatic cancer (Nakayama et al., 2008), and prostate cancer (Hong et al., 2009).\nThe first WW domain of WWOX may interact with proteins possessing a PPxY motif(s) such as AP-2γ, p73, ErbB4, Ezrin, SIMPLE, c-Jun, RUNX4, and many others (Chang et al., 2007; Salah et al., 2012; Su et al., 2012; Figure 1). Transiently overexpressed WWOX binds transcription factors AP-2, p73, and c-Jun and block their nuclear relocation in vitro, which suppresses cancer cell survival (Salah et al., 2012). In stark contrast, Wwox co-migrates with proapoptotic and pro-survival transcription factors to the nuclei of neurons upon sciatic nerve axotomy in rats (Li et al., 2009). No blocking of translocation of transcription factors to the nuclei by Wwox was observed.\nUnder stress conditions, WWOX is activated via phosphorylation at Tyr33, and binds proteins independently of the PPxY motif (Chang et al., 2001, 2003, 2005a,b, 2007, 2010). Activated WWOX physically interacts with serine 46-phosphorylated p53 (Figure 1), which stabilizes p53 and its apoptotic function (Chang et al., 2005b). Also, WWOX binds Disheveled proteins (Dvl), which are key components in Wnt/β-catenin signaling pathway (Figure 1). No PPxY motif is in Dvl. Transiently overexpressed WWOX sequesters Dvl-2 in the cytoplasm and thereby blocks Dvl-2-mediated TCF transcriptional activity (Bouteille et al., 2009).\nOverexpressed WWOX induces apoptosis and inhibits proliferation of human hepatic carcinoma cells (Hu et al., 2012) and many cancer cell types (Chang et al., 2007, 2010; Salah et al., 2012; Su et al., 2012). WWOX enhances the cytotoxic function of tumor necrosis factor by down-regulating apoptosis inhibitor Bcl-2 and Bcl-xL and up-regulating apoptotic p53 (Chang et al., 2001). Also, WWOX mediates cell death synergistically with p53. Upon exposure to chemicals or environmental stress, such as UV irradiation and chemotherapeutic drugs, WWOX undergoes phosphorylation in Tyr33 and probably others sites, followed by relocating to mitochondria or nuclei for inducing apoptosis (Chang et al., 2007, 2010).\nWWOX binds MEK in Jurkat T cells (Lin et al., 2011). Phorbol myristate acetate (PMA) dissociates the MEK/WWOX complex and induces WWOX to translocate to the mitochondria to induce apoptosis, whereas MEK relocates to the lipid raft. Inhibition of MEK activity increases TMZ-induced suppression of cancer cell growth (Holt et al., 2012). Ectopic expression of WWOX in A549 cells induces procaspase-3 and procaspase-9 activation and induces cytochrome C releasing from the mitochondria (Zhang et al., 2012a). Complement C1q induces ectopic WWOX phosphorylation in Try33 and leads to cell apoptosis independently of the classical complement activation pathway (Hong et al., 2009). A portion of WWOX is anchored in the membrane/cytoskeleton area via binding with hyaluronidase Hyal-2 (Hsu et al., 2009) and Phospho-Ezrin (Jin et al., 2006). Transforming growth factor β1 binds Hyal-2 as a cognate receptor to signal the formation of the WWOX/Hyal-2/Smad4 complex to relocate to the nucleus for enhancing the SMAD-driven promoter activity (Hsu et al., 2009)."}

pmc-enju-pas

2_test

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T12774","span":{"begin":2475,"end":2479},"obj":"http://purl.obolibrary.org/obo/UBERON_3000101"},{"id":"T12773","span":{"begin":2317,"end":2321},"obj":"http://purl.obolibrary.org/obo/UBERON_3000101"},{"id":"T12772","span":{"begin":2211,"end":2215},"obj":"http://purl.obolibrary.org/obo/UBERON_3000101"},{"id":"T12771","span":{"begin":1161,"end":1164},"obj":"http://purl.obolibrary.org/obo/UBERON_2000711"},{"id":"T3814","span":{"begin":545,"end":549},"obj":"http://purl.obolibrary.org/obo/UBERON_0002415"},{"id":"T3822","span":{"begin":6104,"end":6108},"obj":"http://purl.obolibrary.org/obo/UBERON_3000101"},{"id":"T3821","span":{"begin":6039,"end":6043},"obj":"http://purl.obolibrary.org/obo/UBERON_3000101"},{"id":"T3820","span":{"begin":5939,"end":5943},"obj":"http://purl.obolibrary.org/obo/UBERON_3000101"},{"id":"T3819","span":{"begin":3709,"end":3714},"obj":"http://purl.obolibrary.org/obo/UBERON_0001021"},{"id":"T3818","span":{"begin":3701,"end":3714},"obj":"http://purl.obolibrary.org/obo/UBERON_0001322"},{"id":"T3817","span":{"begin":2892,"end":2898},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"T3816","span":{"begin":3051,"end":3055},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T3815","span":{"begin":2713,"end":2717},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"WW Domain-Containing Oxidoreductase WWOX\nRecently, tumor suppressors p53 and WWOX were shown to regulate the apoptosis of glioblastoma cells (Chiang et al., 2012). WW domain-containing oxidoreductase, known as WWOX, FOR, or WOX1, is encoded by human or mouse WWOX/Wwox gene. This gene is located in chromosome 16q23.3–24.1, an area known as the common fragile site FRA16D. The full-length WWOX protein is composed of two N-terminal WW domains, a C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, and a proapoptotic C-terminal tail D3 (Chang et al., 2001, 2007, 2010; Aqeilan et al., 2004, 2007; Hong et al., 2007; Salah et al., 2012) (Figure 1). WWOX may act as an alternative receptor for sex steroid hormones, since its SDR domain possesses an NSYK motif capable of interacting with androgen and estrogen (Chang et al., 2005a; Su et al., 2012).\nFigure 1 Schematic diagrams of WWOX structure and its role in signaling. WWOX contains two N-terminal WW domains, a C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, and a D3 region. A nuclear localization signal (NLS) is in between the WW domains (Chang et al., 2003, 2007; Del Mare et al., 2011; Salah et al., 2012; Su et al., 2012; reviews). The SDR domain possesses a mitochondria-binding region. There are two conserved tyrosine phosphorylation sites, Tyr33 and Tyr287. Other phosphorylation sites predicted by NetPhos 2.0 Server are Tyr6, Thr12, Ser14, Tyr61, Tyr293, and Thr3B3, respectively. Upon stress stimulation, WWOX is phosphorylated in Tyr33 and binds p53. The WWOX/p53 complex then translocates to mitochondria or nucleus to induce apoptosis. WWOX also binds PPxY motif-containing transcription factors, such as RUNX2, c-Jun, and ERBB4, via its first WW domain, and the binding blocks the activity of these proteins by retaining them in the cytoplasm. WWOX binds Tau via its SDR domain. WWOX participates in the Wnt/β-catenin signal pathway by binding Dvl and inhibiting its nuclear import. Phorbol ester stimulates the dissociation of MEK/WWOX complex in Jurkat T cell, and the released WWOX translocates to the mitochondria for causing cell death. WWOX is recruited to the membrane area by association with Hyal-2 and phospho-Ezrin. Hyal-2 is an alternative receptor for TGF-β1. In response to TGF-β1, WWOX binds Hyal-2 and forms a complex, followed by relocating to the nucleus and enhancing the SMAD-driven promoter activity. Ack1, activated Cdc42-associated kinase 1; Hyal-2, hyaluronoglucosaminidase 2; CKI, casein kinase; GSK, glycogen synthase kinase; PKA, protein kinase A. Expression of WWOX is either altered or lost from epigenetic modification in multiple malignant cancers, such as non-small cell lung carcinoma (Donati et al., 2007), hematopoietic malignancies (Ishii and Furukawa, 2004), gastric carcinoma (Aqeilan et al., 2004), pancreatic carcinoma (Kuroki et al., 2004), breast carcinoma (Guler et al., 2004; Aqeilan et al., 2007), and glioblastoma multiforme (Kosla et al., 2011). Restoration of WWOX gene prevents the growth of lung cancer (Fabbri et al., 2005), pancreatic cancer (Nakayama et al., 2008), and prostate cancer (Hong et al., 2009).\nThe first WW domain of WWOX may interact with proteins possessing a PPxY motif(s) such as AP-2γ, p73, ErbB4, Ezrin, SIMPLE, c-Jun, RUNX4, and many others (Chang et al., 2007; Salah et al., 2012; Su et al., 2012; Figure 1). Transiently overexpressed WWOX binds transcription factors AP-2, p73, and c-Jun and block their nuclear relocation in vitro, which suppresses cancer cell survival (Salah et al., 2012). In stark contrast, Wwox co-migrates with proapoptotic and pro-survival transcription factors to the nuclei of neurons upon sciatic nerve axotomy in rats (Li et al., 2009). No blocking of translocation of transcription factors to the nuclei by Wwox was observed.\nUnder stress conditions, WWOX is activated via phosphorylation at Tyr33, and binds proteins independently of the PPxY motif (Chang et al., 2001, 2003, 2005a,b, 2007, 2010). Activated WWOX physically interacts with serine 46-phosphorylated p53 (Figure 1), which stabilizes p53 and its apoptotic function (Chang et al., 2005b). Also, WWOX binds Disheveled proteins (Dvl), which are key components in Wnt/β-catenin signaling pathway (Figure 1). No PPxY motif is in Dvl. Transiently overexpressed WWOX sequesters Dvl-2 in the cytoplasm and thereby blocks Dvl-2-mediated TCF transcriptional activity (Bouteille et al., 2009).\nOverexpressed WWOX induces apoptosis and inhibits proliferation of human hepatic carcinoma cells (Hu et al., 2012) and many cancer cell types (Chang et al., 2007, 2010; Salah et al., 2012; Su et al., 2012). WWOX enhances the cytotoxic function of tumor necrosis factor by down-regulating apoptosis inhibitor Bcl-2 and Bcl-xL and up-regulating apoptotic p53 (Chang et al., 2001). Also, WWOX mediates cell death synergistically with p53. Upon exposure to chemicals or environmental stress, such as UV irradiation and chemotherapeutic drugs, WWOX undergoes phosphorylation in Tyr33 and probably others sites, followed by relocating to mitochondria or nuclei for inducing apoptosis (Chang et al., 2007, 2010).\nWWOX binds MEK in Jurkat T cells (Lin et al., 2011). Phorbol myristate acetate (PMA) dissociates the MEK/WWOX complex and induces WWOX to translocate to the mitochondria to induce apoptosis, whereas MEK relocates to the lipid raft. Inhibition of MEK activity increases TMZ-induced suppression of cancer cell growth (Holt et al., 2012). Ectopic expression of WWOX in A549 cells induces procaspase-3 and procaspase-9 activation and induces cytochrome C releasing from the mitochondria (Zhang et al., 2012a). Complement C1q induces ectopic WWOX phosphorylation in Try33 and leads to cell apoptosis independently of the classical complement activation pathway (Hong et al., 2009). A portion of WWOX is anchored in the membrane/cytoskeleton area via binding with hyaluronidase Hyal-2 (Hsu et al., 2009) and Phospho-Ezrin (Jin et al., 2006). Transforming growth factor β1 binds Hyal-2 as a cognate receptor to signal the formation of the WWOX/Hyal-2/Smad4 complex to relocate to the nucleus for enhancing the SMAD-driven promoter activity (Hsu et al., 2009)."}

GO-BP

GO-MF

{"project":"GO-MF","denotations":[{"id":"T12929","span":{"begin":2562,"end":2565},"obj":"http://purl.obolibrary.org/obo/GO_0004691"},{"id":"T12928","span":{"begin":2531,"end":2534},"obj":"http://purl.obolibrary.org/obo/GO_0050321"},{"id":"T12927","span":{"begin":1753,"end":1779},"obj":"http://purl.obolibrary.org/obo/GO_0050699"},{"id":"T12926","span":{"begin":1946,"end":1953},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T12925","span":{"begin":1772,"end":1779},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T12924","span":{"begin":1271,"end":1278},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T4076","span":{"begin":5912,"end":5919},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T4075","span":{"begin":5865,"end":5873},"obj":"http://purl.obolibrary.org/obo/GO_0043495"},{"id":"T4071","span":{"begin":5605,"end":5615},"obj":"http://purl.obolibrary.org/obo/GO_0045155"},{"id":"T4070","span":{"begin":5605,"end":5615},"obj":"http://purl.obolibrary.org/obo/GO_0045154"},{"id":"T4069","span":{"begin":5605,"end":5615},"obj":"http://purl.obolibrary.org/obo/GO_0045153"},{"id":"T4068","span":{"begin":5413,"end":5425},"obj":"http://purl.obolibrary.org/obo/GO_0004708"},{"id":"T4067","span":{"begin":4708,"end":4729},"obj":"http://purl.obolibrary.org/obo/GO_0043120"},{"id":"T4066","span":{"begin":4708,"end":4729},"obj":"http://purl.obolibrary.org/obo/GO_0005164"},{"id":"T4074","span":{"begin":5605,"end":5615},"obj":"http://purl.obolibrary.org/obo/GO_0045158"},{"id":"T4073","span":{"begin":5605,"end":5615},"obj":"http://purl.obolibrary.org/obo/GO_0045157"},{"id":"T4072","span":{"begin":5605,"end":5615},"obj":"http://purl.obolibrary.org/obo/GO_0045156"}],"text":"WW Domain-Containing Oxidoreductase WWOX\nRecently, tumor suppressors p53 and WWOX were shown to regulate the apoptosis of glioblastoma cells (Chiang et al., 2012). WW domain-containing oxidoreductase, known as WWOX, FOR, or WOX1, is encoded by human or mouse WWOX/Wwox gene. This gene is located in chromosome 16q23.3–24.1, an area known as the common fragile site FRA16D. The full-length WWOX protein is composed of two N-terminal WW domains, a C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, and a proapoptotic C-terminal tail D3 (Chang et al., 2001, 2007, 2010; Aqeilan et al., 2004, 2007; Hong et al., 2007; Salah et al., 2012) (Figure 1). WWOX may act as an alternative receptor for sex steroid hormones, since its SDR domain possesses an NSYK motif capable of interacting with androgen and estrogen (Chang et al., 2005a; Su et al., 2012).\nFigure 1 Schematic diagrams of WWOX structure and its role in signaling. WWOX contains two N-terminal WW domains, a C-terminal short-chain alcohol dehydrogenase/reductase (SDR) domain, and a D3 region. A nuclear localization signal (NLS) is in between the WW domains (Chang et al., 2003, 2007; Del Mare et al., 2011; Salah et al., 2012; Su et al., 2012; reviews). The SDR domain possesses a mitochondria-binding region. There are two conserved tyrosine phosphorylation sites, Tyr33 and Tyr287. Other phosphorylation sites predicted by NetPhos 2.0 Server are Tyr6, Thr12, Ser14, Tyr61, Tyr293, and Thr3B3, respectively. Upon stress stimulation, WWOX is phosphorylated in Tyr33 and binds p53. The WWOX/p53 complex then translocates to mitochondria or nucleus to induce apoptosis. WWOX also binds PPxY motif-containing transcription factors, such as RUNX2, c-Jun, and ERBB4, via its first WW domain, and the binding blocks the activity of these proteins by retaining them in the cytoplasm. WWOX binds Tau via its SDR domain. WWOX participates in the Wnt/β-catenin signal pathway by binding Dvl and inhibiting its nuclear import. Phorbol ester stimulates the dissociation of MEK/WWOX complex in Jurkat T cell, and the released WWOX translocates to the mitochondria for causing cell death. WWOX is recruited to the membrane area by association with Hyal-2 and phospho-Ezrin. Hyal-2 is an alternative receptor for TGF-β1. In response to TGF-β1, WWOX binds Hyal-2 and forms a complex, followed by relocating to the nucleus and enhancing the SMAD-driven promoter activity. Ack1, activated Cdc42-associated kinase 1; Hyal-2, hyaluronoglucosaminidase 2; CKI, casein kinase; GSK, glycogen synthase kinase; PKA, protein kinase A. Expression of WWOX is either altered or lost from epigenetic modification in multiple malignant cancers, such as non-small cell lung carcinoma (Donati et al., 2007), hematopoietic malignancies (Ishii and Furukawa, 2004), gastric carcinoma (Aqeilan et al., 2004), pancreatic carcinoma (Kuroki et al., 2004), breast carcinoma (Guler et al., 2004; Aqeilan et al., 2007), and glioblastoma multiforme (Kosla et al., 2011). Restoration of WWOX gene prevents the growth of lung cancer (Fabbri et al., 2005), pancreatic cancer (Nakayama et al., 2008), and prostate cancer (Hong et al., 2009).\nThe first WW domain of WWOX may interact with proteins possessing a PPxY motif(s) such as AP-2γ, p73, ErbB4, Ezrin, SIMPLE, c-Jun, RUNX4, and many others (Chang et al., 2007; Salah et al., 2012; Su et al., 2012; Figure 1). Transiently overexpressed WWOX binds transcription factors AP-2, p73, and c-Jun and block their nuclear relocation in vitro, which suppresses cancer cell survival (Salah et al., 2012). In stark contrast, Wwox co-migrates with proapoptotic and pro-survival transcription factors to the nuclei of neurons upon sciatic nerve axotomy in rats (Li et al., 2009). No blocking of translocation of transcription factors to the nuclei by Wwox was observed.\nUnder stress conditions, WWOX is activated via phosphorylation at Tyr33, and binds proteins independently of the PPxY motif (Chang et al., 2001, 2003, 2005a,b, 2007, 2010). Activated WWOX physically interacts with serine 46-phosphorylated p53 (Figure 1), which stabilizes p53 and its apoptotic function (Chang et al., 2005b). Also, WWOX binds Disheveled proteins (Dvl), which are key components in Wnt/β-catenin signaling pathway (Figure 1). No PPxY motif is in Dvl. Transiently overexpressed WWOX sequesters Dvl-2 in the cytoplasm and thereby blocks Dvl-2-mediated TCF transcriptional activity (Bouteille et al., 2009).\nOverexpressed WWOX induces apoptosis and inhibits proliferation of human hepatic carcinoma cells (Hu et al., 2012) and many cancer cell types (Chang et al., 2007, 2010; Salah et al., 2012; Su et al., 2012). WWOX enhances the cytotoxic function of tumor necrosis factor by down-regulating apoptosis inhibitor Bcl-2 and Bcl-xL and up-regulating apoptotic p53 (Chang et al., 2001). Also, WWOX mediates cell death synergistically with p53. Upon exposure to chemicals or environmental stress, such as UV irradiation and chemotherapeutic drugs, WWOX undergoes phosphorylation in Tyr33 and probably others sites, followed by relocating to mitochondria or nuclei for inducing apoptosis (Chang et al., 2007, 2010).\nWWOX binds MEK in Jurkat T cells (Lin et al., 2011). Phorbol myristate acetate (PMA) dissociates the MEK/WWOX complex and induces WWOX to translocate to the mitochondria to induce apoptosis, whereas MEK relocates to the lipid raft. Inhibition of MEK activity increases TMZ-induced suppression of cancer cell growth (Holt et al., 2012). Ectopic expression of WWOX in A549 cells induces procaspase-3 and procaspase-9 activation and induces cytochrome C releasing from the mitochondria (Zhang et al., 2012a). Complement C1q induces ectopic WWOX phosphorylation in Try33 and leads to cell apoptosis independently of the classical complement activation pathway (Hong et al., 2009). A portion of WWOX is anchored in the membrane/cytoskeleton area via binding with hyaluronidase Hyal-2 (Hsu et al., 2009) and Phospho-Ezrin (Jin et al., 2006). Transforming growth factor β1 binds Hyal-2 as a cognate receptor to signal the formation of the WWOX/Hyal-2/Smad4 complex to relocate to the nucleus for enhancing the SMAD-driven promoter activity (Hsu et al., 2009)."}

GO-CC

sentences

simple1

PMC:3586680 / 6635-12854 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:3586680 / 6635-12854 JSON TXT