Ebp1, an ErbB‐3 binding protein, interacts with Rb and affects Rb transcriptional regulation

Xia, Xianmin; Cheng, Ann‐Lii; Lessor, Tracy; Zhang, Yuexing; Hamburger, Anne W.

doi:10.1002/jcp.1075

Cited by 84 publications

(147 citation statements)

References 25 publications

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“…The data in Figure 5A demonstrate that the GFP mutants were expressed at approximately equal levels. ErbB3 binding protein has previously been reported to be primarily localised in the nucleolus and cytoplasm, with weak nucleoplasmic staining (Xia et al, 2001;Squatrito et al, 2004;Ahn et al, 2006). The subcellular localisation of Ebp1 was not altered by mutation of T261 as demonstrated by immunofluorescence microscopy ( Figure 5B).…”

Section: P21-activated Kinase 1 Regulation Of Ebp1 Corepressor Functionsmentioning

confidence: 60%

“…Flag-Ebp1 was immunoprecipitated from MCF-7 cell lysates using anti-Flag M2 Agarose beads (Sigma) as described previously (Xia et al, 2001). GFP-Ebp1 was immunoprecipitated from cell lysates using anti-GFP Agarose beads (Medical & Biological Laboratories (MBL), Woburn, MA, USA).…”

Section: Immunoprecipitationmentioning

confidence: 99%

“…A total of 5 Â 10 4 MCF-7 cells per well were transfected with 0.5 mg of GFP, GFP-Ebp1, GFP-Ebp1 T261A or GFP-Ebp1 T261E plasmids, 0.5 mg of pE2F1-luc (a firefly luciferase reporter gene under the control of the À225 to þ 1 region of the E2F1 promoter) (Johnson et al, 1994), or a Cyclin D1-luc reporter (1 -163 of the Cyclin D1 promoter) (Xia et al, 2001) and 5 ng of pRL-TK vector (a Renilla luciferase reporter gene under the control of the thymidine kinase promoter) using Fugene 6 (Boerhringer Mannheim). Forty-eight hours after transfection, cells were lysed and luciferase activity determined using a dual-luciferase reporter assay (Promega, Madison, WI, USA).…”

Section: Dual Luciferase Assaymentioning

confidence: 99%

“…ErbB3 binding protein binds ErbB3 in human breast cancer cells Ahn et al, 2006), but dissociates from the receptor in response to HRG . Overexpression of Ebp1 inhibits the transcription of reporter genes controlled by Cyclin D1, Cyclin E and c-myc promoters and the transcription of endogenous E2F1 and c-myc genes via its binding to an E2F1 consensus element (Xia et al, 2001;Zhang et al, 2003;Zhang and Hamburger, 2004). The interaction of Ebp1 with histone deacetylase 2 (HDAC2), Rb and Sin3A is needed for Ebp1 to repress transcription (Zhang et al, 2003Zhang and Hamburger, 2004).…”

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confidence: 99%

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Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells

et al. 2008

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The ErbB3 binding protein (Ebp1) is a transcriptional corepressor that inhibits the activity of proliferation-associated genes and the growth of human breast cancer cell lines. Treatment of breast cancer cells with the ErbB3 ligand heregulin (HRG) results in increased phosphorylation of Ebp1 and transcriptional repression. The p21-activated serine/threonine kinase 1 (PAK1), which plays an important role in breast cancer progression and resistance to the anti-oestrogen tamoxifen, is also activated by HRG. We therefore examined the ability of PAK1 to phosphorylate and regulate the function of Ebp1. We found that PAK1 phosphorylated Ebp1 in vitro and mapped the phosphorylation site to threonine 261. Both HRG treatment and expression of a constitutively activated PAK1 in MCF-7 breast cancer cells enhanced threonine phosphorylation of Ebp1. In MCF-7 cells, ectopically expressed Ebp1 bound endogenous PAK1 and this association was enhanced by treatment with HRG. Mutation of the PAK1 phosphorylation site to glutamic acid, mimicking a phosphorylated state, completely abrogated the ability of Ebp1 to repress transcription, inhibit growth of breast cancer cell lines and contribute to tamoxifen sensitivity. These studies demonstrate for the first time that Ebp1 is a substrate of PAK1 and the importance of the PAK1 phosphorylation site for the functional activity of Ebp1 in breast cancer cells.

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Section: P21-activated Kinase 1 Regulation Of Ebp1 Corepressor Functionsmentioning

confidence: 60%

Section: Immunoprecipitationmentioning

confidence: 99%

Section: Dual Luciferase Assaymentioning

confidence: 99%

mentioning

confidence: 99%

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Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells

et al. 2008

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“…The MMTVluciferase plasmid was obtained from Dr Joseph Fondell (Wang and Fondell, 2001). The ebp1 expression construct has been previous described (Xia et al, 2001a).…”

Section: Plasmidsmentioning

confidence: 99%

Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signalling

Zhang

Hamburger

2004

Br J Cancer

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Although ErbB receptors have been implicated in the progression of prostate cancer, little is known about proteins that may mediate their interactions with the androgen receptor (AR). Ebp1, a protein cloned via its association with the ErbB3 receptor, binds the AR and inhibits androgen-regulated transactivation of wild-type AR in COS cells. As the complement of coregulators in different cells are important for AR activity, we determined the effect of Ebp1 on AR function in prostate cancer cell lines. In addition, we examined the regulation of Ebp1 function by the ErbB3/4 ligand heregulin (HRG). In this study, we demonstrate, using several natural AR-regulated promoters, that Ebp1 repressed transcriptional activation of wild-type AR in prostate cancer cell lines. Downregulation of Ebp1 expression in LNCaP cells using siRNA resulted in activation of AR in the absence of androgen. Ebp1 associated with ErbB3 in LNCaP cells in the absence of HRG, but HRG induced the dissociation of Ebp1 from ErbB3. In contrast, HRG treatment enhanced both the association of Ebp1 with AR and also the ability of Ebp1 to repress AR transactivation. These studies suggest that Ebp1 is an AR corepressor whose biological activity can be regulated by the ErbB3 ligand, HRG.

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The structure and function of multifunctional protein ErbB3 binding protein 1 (Ebp1) and its role in diseases

Wang,

Xing,

Liang

et al. 2024

Cell Biology International

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ErbB3‐binding protein 1(Ebp1) has two isoforms, p42 Ebp1 and p48 Ebp1, both of which can regulate cell growth and differentiation. But these isoforms often have opposite effects, including contradictory roles in regulation of cell growth in different tissues and cells. P48 Ebp1 belongs to the full‐length sequence, while conformational changes in the crystal structure of p42 Ebp1 reveals a lack of an α helix at the amino terminus. Due to the differences in the structures of these two isoforms, they have different binding partners and protein modifications. Ebp1 can function as both an oncogene and a tumor suppressor factor. However, the underlying mechanisms by which these two isoforms exert opposite functions are still not fully understood. In this review, we summarize the genes and the structures of protein of these two isoforms, protein modifications, binding partners and the association of different isoforms with diseases.

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Ebp1, an ErbB‐3 binding protein, interacts with Rb and affects Rb transcriptional regulation

Cited by 84 publications

References 25 publications

Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells

Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells

Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signalling

The structure and function of multifunctional protein ErbB3 binding protein 1 (Ebp1) and its role in diseases

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