WBP-2, a WW domain binding protein, interacts with the thyroid-specific transcription factor Pax8

Nitsch, Roberto; Palma, Tina Di; Mascia, Anna; Zannini, Mariastella

doi:10.1042/bj20031233

Cited by 25 publications

(27 citation statements)

References 56 publications

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“…Additionally, we also found that WBP-2 specifically directly interacts with ER and PR. Our observation that WBP-2 can interact with proteins that do not contain WWdomain is also consistent with a previously published study that suggests WBP-2 interacts with the transcription factor Pax8 [14]. Previously, it has been suggested that WBP-2 act as a transcriptional adaptor for Pax8 [14].…”

Section: Coactivators Of Er and Prsupporting

confidence: 81%

Role of PY Motif Containing Protein, WBP-2 in ER, PR Signaling and Breast Tumorigenesis

Ramamoorthy¹,

Nawaz²

2009

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE 3. DATES COVERED (From -To) PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited SUPPLEMENTARY NOTES ABSTRACTOur data demonstrates that WBP-2 is recruited onto the hormone responsive promoters in the presence of hormone and it specifically enhances the transactivation functions of PR and ER. Our data also demonstrates that WBP-2 contains an intrinsic activation domain and the cPPXY of WBP-2 is essential for its coactivation and intrinsic activation functions. Our preliminary data also demonstrates that the WBP-2 binding protein, YAP1 enhances PR and ER transactivation but YAP1's coactivation function is absolutely dependent on WBP-2. Furthermore, cPPXY motif of WBP-2 and WW-domain of YAP1 is required for YAP1 to work as a transcriptional coactiva-tor. Additionally, our data also indicate that the coactivation functions of WBP-2 and YAP1 are suppressed by WWOX1, suggesting that WWOX1 may regulates the transactivation functions of ER and PR by antagonizing the functions of WBP-2 and YAP1. Taken together our data estab-lished the role of WBP-2 and YAP1 as coactivators and WWOX1 as a repressor for ER and PR transactivation pathways.

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Section: Coactivators Of Er and Prsupporting

confidence: 81%

Role of PY Motif Containing Protein, WBP-2 in ER, PR Signaling and Breast Tumorigenesis

Ramamoorthy¹,

Nawaz²

2009

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“…As previously shown by RT-PCR and Western blot experiments (Figs. 1A, B) c-Myc 9E10 (Santa Cruz Biotechnology) recognizing the Myc-tag fused to DREAM and with anti-Pax8 [30] (Fig. 6).…”

Section: Dream Inhibits Endogenous Pax8 Expression In a Physiologicalmentioning

confidence: 99%

“…Primary antibodies were the following: rabbit polyclonal anti-Pax8 [30], and anti-c-myc (9E10) mAb from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA).…”

Section: Indirect Immunofluorescence and Confocal Scanning Laser Micrmentioning

confidence: 99%

“…Gels were blotted onto Immobilon P (Millipore, Bredford, MA, USA) for 16-18 h and the membranes were blocked in 5% nonfat dry milk for 2 h at room temperature. Immunodetection was performed using specific antibodies against Pax8 [30], TTF-1 [17], Foxe1 [21], Tg [31], DREAM (kindly provided by J.R. Naranjo), cyclin D3 (C-16) (Santa Cruz, CA), p27 and CdK2 (Transduction Laboratories), and a-tubulin (Sigma) proteins. Subsequently, the filters were developed using an enhanced chemiluminescence detection method (Pierce) according to the manufacturer's directions.…”

Section: Protein Extracts and Western Blotmentioning

confidence: 99%

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The transcriptional repressor DREAM is involved in thyroid gene expression

D’Andrea

Palma

Mascia

et al. 2005

Experimental Cell Research

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“…WBP2-deficient mice exhibit a progressive highfrequency hearing loss, which may be due to the coactivation of WBP2 on the estrogen receptor α (ESR1) and the progesterone receptor (PGR) [7]. In addition, WBP2 behaves as an adaptor molecule of Pax8 [8], which is essential for the differentiation of thyroid cells [9]. It can also interact with YAP/TAZ as a bridge linking Hippo and Wnt pathways in breast cancer [10].…”

Section: Introductionmentioning

confidence: 99%

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

Song¹,

Wu²,

Xie³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dysregulated expression of WW domain-binding protein 2 (WBP2) is associated with poor prognosis in ER+ breast cancer patients. However, its role in triple negative breast cancer (TNBC) has not been previously assessed. Therefore, we aimed to elucidate the functional mechanism of WBP2 in TNBC cells. Methods: qRT-PCR, western blotting, and immunohistochemical staining were used to evaluate WBP2 expression in TNBC patient tumors and cell lines. HCC1937 and MDA-MB-231 cells transiently transfected with WBP2 small interfering RNA (siRNA), miR-613 mimics, or miR-613 inhibitors were subject to assays for cell viability, apoptosis and cell cycle distribution. Co-immunoprecipitation, western blotting or qRT-PCR were employed to monitor changes in signaling pathway-related genes and proteins. Luciferase assays were performed to assess whether WBP2 is a direct target of miR-613. The effect of miR-613 on tumor growth was assessed in vivo using mouse xenograft models. Results: The expression of WBP2 was upregulated in TNBC tissues and cells. Expression of WBP2 was significantly correlated with Ki67 in TNBC patients. Knockdown of WBP2 inhibited cellular proliferation, promoted apoptosis, and induced cell cycle arrest of TNBC cells. miR-613 directly bound to the 3’-untranslated region (3’-UTR) of WBP2 and regulated the expression of WBP2. Moreover, miR-613 reduced the expression of WBP2 and suppressed tumor growth of TNBC cells in vivo. Knockdown of WBP2 inhibited YAP transcription and the EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by inhibition of miR-613. Conclusion: WBP2 overexpression is associated with the poor prognosis of TNBC patients and the miR-613-WBP2 axis represses TNBC cell growth by inactivating YAP-mediated gene expression and the EGFR/PI3K/Akt signaling pathway.

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WBP-2, a WW domain binding protein, interacts with the thyroid-specific transcription factor Pax8

Cited by 25 publications

References 56 publications

Role of PY Motif Containing Protein, WBP-2 in ER, PR Signaling and Breast Tumorigenesis

Role of PY Motif Containing Protein, WBP-2 in ER, PR Signaling and Breast Tumorigenesis

The transcriptional repressor DREAM is involved in thyroid gene expression

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

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