A Structure-based Model of the c-Myc/Bin1 Protein Interaction Shows Alternative Splicing of Bin1 and c-Myc Phosphorylation are Key Binding Determinants

Pineda‐Lucena, Antonio; Ho, Cynthia S.W.; Mao, Daniel Y.L.; Sheng, Yi; Laister, Rob C.; Muhandiram, Ranjith; Lu, Ying; Seet, Bruce T.; Katz, Sigal; Szyperski, Thomas; Penn, Linda Z.; Arrowsmith, C.H.

doi:10.1016/j.jmb.2005.05.046

Cited by 97 publications

(114 citation statements)

References 42 publications

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“…[15][16][17][18] While BAR adapter proteins have a canonical function in vesicle dynamics, 19 in certain family members that localize to the nucleus, e.g., Bin1 and APPL proteins, an additional 'moonlighting function' in transcriptional regulation appears to exist. 4,5,20 Notably, only those Bin1 isoforms capable of nuclear localization are capable of suppressing oncogenic transformation, facilitating cell suicide, and promoting immune escape of transformed cells in mouse model systems. 3,4,8,14,[21][22][23][24][25] Thus, it is conceivable that attenuated expression or nuclear exclusion in breast tumor cells that leads to inactivation of these activities may be sufficient to convey prognostic information for exploitation.…”

Section: Resultsmentioning

confidence: 99%

“…1,2 Bin1 has properties of a negative modifier gene, encoding a nucleocytosolic BAR adapter protein that can interact with c-Myc and inhibit its cell transforming activity. [3][4][5] c-Myc is involved in the development of many human breast cancers where its overexpression has been associated with poor prognosis. 6 Notably, targeted deletion of Bin1 in the mouse mammary gland can cooperate with ras activation to drive tumor progression.…”

Section: Introductionmentioning

confidence: 99%

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Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival

Ghaneie¹,

Zemba-Palko²,

Itoh³

et al. 2007

Cancer Biology & Therapy

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Clinical outcomes in breast cancer are likely influenced by modifier genes that affect tumor dormancy versus progression. The Bin1 gene encodes a nucleocytosolic adapter protein that suppresses neoplastic cell transformation and that is often attenuated in human breast carcinoma. Recent mouse genetic studies indicate that Bin1 loss cooperates with ras activation to drive progression of mammary carcinoma, establishing Bin1 as a negative modifier of tumor progression in breast cancer. In this study, we investigated whether immunohistochemical losses of nuclear Bin1 proteins in cases of human breast cancer were correlated to progression status. In American and Japanese groups of low or middle grade breast cancers, losses were associated with reduced survival and increased nodal metastasis, respectively. Taken together with recent findings from mouse genetic studies, these findings encourage further evaluation of the potential utility of Bin1 as a clinical prognostic marker in breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival

Ghaneie¹,

Zemba-Palko²,

Itoh³

et al. 2007

Cancer Biology & Therapy

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show abstract

“…Bin1 encodes a nucleocytosolic BAR adapter protein that can interact with the c-Myc oncoprotein and inhibit its cell transforming activity (1)(2)(3). c-Myc is involved in the development of many human cancers where its overexpression is associated with poor prognosis (4).…”

Section: Introductionmentioning

confidence: 99%

“…Multiple splice isoforms of Bin1 exist with diverse patterns of tissue distribution, subcellular localization, and protein interactions (5)(6)(7)(8). Although BAR adapter proteins share canonical functions in membrane dynamics (9), certain BAR proteins, such as those encoded by the Bin1 and APPL genes, may also have functions in transcriptional control (2,3,10). Notably, only nuclear-localizing isoforms of Bin1 can restrict proliferation, survival, and immune escape of oncogenically transformed cells (1,2,(11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Bin1 Ablation Increases Susceptibility to Cancer during Aging, Particularly Lung Cancer

et al. 2007

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Age is the major risk factor for cancer, but few genetic pathways that modify cancer incidence during aging have been described. Bin1 is a prototypic member of the BAR adapter gene family that functions in vesicle dynamics and nuclear processes. Bin1 limits oncogenesis and is often attenuated in human cancers, but its role in cancer suppression has yet to be evaluated fully in vivo. In the mouse, homozygous deletion of Bin1 causes developmental lethality, so to assess this role, we examined cancer incidence in mosaic null mice generated by a modified Cre-lox technology. During study of these animals, one notable phenotype was an extended period of female fecundity during aging, with mosaic null animals retaining reproductive capability until the age of 17.3 F 1.1 months. Through 1 year of age, cancer incidence was unaffected by Bin1 ablation; however, by 18 to 20 months of age, f50% of mosaic mice presented with lung adenocarcinoma and f10% with hepatocarcinoma. Aging mosaic mice also displayed a higher incidence of inflammation and/or premalignant lesions, especially in the heart and prostate. In mice where colon tumors were initiated by a ras-activating carcinogen, Bin1 ablation facilitated progression to more aggressive invasive status. In cases of human lung and colon cancers, immunohistochemical analyses evidenced frequent attenuation of Bin1 expression, paralleling observations in other solid tumors. Taken together, our findings highlight an important role for Bin1 as a negative modifier of inflammation and cancer susceptibility during aging. [Cancer Res 2007;67(16):7605-12]

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“…Bin1 is a member of the Bin amphiphysin rys (BAR) adaptor family with myriad biological functions, including cytoskeletal organization, tumor suppression, transcriptional regulation, and DNA repair [15,16]. Bin1 homologs are found in yeast and Caenorhabditis elegans, supporting the argument for evolutionary conservation of function (reviewed in [17]).…”

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confidence: 98%

Bin1: A New Player in IBD Barrier Dysfunction

Ryu

Posca

2012

Dig Dis Sci

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A Structure-based Model of the c-Myc/Bin1 Protein Interaction Shows Alternative Splicing of Bin1 and c-Myc Phosphorylation are Key Binding Determinants

Cited by 97 publications

References 42 publications

Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival

Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival

Bin1 Ablation Increases Susceptibility to Cancer during Aging, Particularly Lung Cancer

Bin1: A New Player in IBD Barrier Dysfunction

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