The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42

Oliver, Anthony W.; He, Xiaotong; Borthwick, Katherine; Donne, Adam; Hampson, Lynne; Hampson, Ian N.

doi:10.1038/sj.bjc.6606026

Cited by 38 publications

(43 citation statements)

References 35 publications

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“…Although more studies are needed to elucidate the mechanism(s), TIP-1 likely controls secretion of those angiogenic factors. Several TIP-1-interacting proteins, such as such as β-catenin [7], Rhotekin [9], and ARHGEF16 [12], are directly or indirectly involved in the activation of Rho GTPases for protein secretion [43; 44]. Roles of TIP-1 in the glioblastoma formation and growth and its proposed mechanisms of action were summarized in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…TIP-1 involves in a wide spectrum of biological processes through selective protein interactions, such as beta-catenin [7], brain-specific angiogenesis inhibitor 2 [8], rhotekin [9], HPV16 E6 [10], HTLV-1 Tax [11], ARHGEF16 [12], potassium channel Kir2.3 [13], and glutaminase [14]. TIP-1 has been reported to regulate gastrulation movements during zebrafish embryo development [6].…”

Section: Introductionmentioning

confidence: 99%

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Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice

Han¹,

Wang²,

Zhang³

et al. 2013

Cancer Letters

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Glioblastoma is the most common and fatal type of primary brain tumors featured with hyperplastic blood vessels. Here, we performed meta-analyses of published data and established a correlation between high TIP-1 expression levels and the poor prognosis of glioblastoma patients. Next, we explored the biological relevance of TIP-1 expression in the pathogenesis of glioblastoma. By using orthotopic and heterotopic mouse models of human glioblastomas, this study has characterized TIP-1 as one contributing factor to the tumor-driven angiogenesis. In vitro and in vivo functional assays, along with biochemical analyses with microarrays and antibody arrays, have demonstrated that TIP-1 utilizes multiple pathways including modulating fibronectin gene expression and uPA protein secretion, to establish or maintain a pro-angiogenic microenvironment within human glioblastoma. In conclusion, this work supports the hypothesis that TIP-1 represents a novel prognostic biomarker and a therapeutic target of human glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice

Han¹,

Wang²,

Zhang³

et al. 2013

Cancer Letters

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“…According to previous studies, [14] Plexin D1 has been connected to Tip-1, which was established as an interactor of E6, which is the cervical cancer oncogene. [15] To further investigate the possible role of Plexin D1 in the cervical cancer progression, we decided to study the expression of this gene in various cervical cancer stages. Previous studies [16] used in situ hybridization to establish expression of Plexin D1 in solid malignancies; our study aimed to confirm the previous results.…”

Section: Introductionmentioning

confidence: 99%

Plexin D1: New Potential Biomarker for Cervical Cancer

Shalaby

Hampson

Oliver

et al. 2012

Journal of Immunoassay and Immunochemistry

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To explore possible role of Plexin D1 in cancer angiogenesis with special focus on cervical cancer. Twelve various normal tissues, 12 various tumor samples, and 59 different stages of cervical cancer samples on tissue microarrays were examined for the expression of Plexin D1. The findings of our study clearly indicate that Plexin D1 is strongly associated with cellular differentiation in the tissues investigated, and that expression is strongly dependent on the tumor histotype. In some tumor subtypes, the protein was detected at several-fold higher levels than was found in the corresponding normal tissues, while in others, expression was similar to normal tissues. Most significantly, strong expression was detected in the endothelial cells of the cervical cancer samples, yet no expression was seen in endothelial cells of normal cervical tissues, which suggests a potential role of Plexin D1 in cervical cancer-associated angiogenesis.Regarding the implications of Plexin D1 and its associations with cancer angiogenesis, it might be a potential cervical cancer biomarker if further studies confirm the present preliminary findings.

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“…Furthermore it is the target of two separate tumor viruses (HTLV1 and HPV16). It has also been very recently shown that Tip-1 interacts with HP1616 E6 and the guanidine exchange factor Gef16 to activate Cdec42 (Oliver et al, 2011). Taking these findings in conjunction with the previously reported roles of Tip-1 in both Rho and Wnt signaling, this clearly indicates that Tip-1 is an important "hub" protein.…”

Section: Discussionmentioning

confidence: 61%

“…It was first identified by its interaction with the Human T-cell Lymphotrophic Virus, type 1 Tax protein (Olalla et al, 2001) and Tip-1 has also been shown to interact with glutaminase L (Olalla et al, 2001), Rhotekin (Reynaud et al, 2000), β-catenin (Kanamori et al, 2003), Kir 2.3 (Alewine et al, 2006), HPV16 E6 (Hampson et al, 2004) and GEF16 (Oliver et al, 2011). Tip-1 protein was considered of particular interest because it has been reported to interact with two viral oncogenes (E6 and Tax) (Hampson et al, 2004;Rousset et al, 1998).…”

Section: Introductionmentioning

confidence: 98%

Identification of PlexinD1 and AHDC1 as a putative interactors for Tip-1 protein

et al. 2011

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The class 1 PDZ domain Tip-1 protein was first identified as a binding partner for the Human T-Cell Leukaemia Virus type 1 (HTLV-1) Tax oncoprotein. It was later shown to interact with: the RhoA signaling effector Rhotekin, the Wnt signaling effector β-catenin and the E6 oncoprotein from high-risk HPV16 but not low-risk HPV6. These observations suggested that Tip-1 may be an important "hub" protein that is involved in pathways with a proven link to carcinogenesis. Based on these findings, it was decided to further characterize the cellular role of Tip-1 by carrying out a yeast two-hybrid screen to identify new binding partners in order to uncover potentially novel functions of this protein. This identified an intracellular fragment of the trans-membrane receptor plexin D1 and a C-terminal fragment of the AT hook DNA binding containing 1 (AHDC1) protein which had a carboxyl terminal PDZ binding domain consensus sequence. Both of these interactions were confirmed by yeast mating assay which was also used to show that mutant constructs of AHDC1 lacking the carboxyl PDZ binding site did not bind Tip-1. Immunofluorescent imaging of these proteins in HPV16 E6 expressing human C33A cervical carcinoma cells suggested they may co-localize.

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The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42

Cited by 38 publications

References 35 publications

Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice

Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice

Plexin D1: New Potential Biomarker for Cervical Cancer

Identification of PlexinD1 and AHDC1 as a putative interactors for Tip-1 protein

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