Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of β-catenin

Fagotto, François; Glück, Ursula; Gumbiner, Barry M.

doi:10.1016/s0960-9822(98)70082-x

Cited by 400 publications

(319 citation statements)

References 60 publications

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“…The mechanism responsible for nuclear import of MUC1-C is not known, although MUC1-C associates with importin a and h, which function in transporting proteins to the nuclear pore. 1 h-Catenin is transported into the nucleus in the absence of importins and by a mechanism involving direct binding to the nuclear pore complex (56,57). Thus, it is presently unclear whether MUC1-C and h-catenin are transported into the nucleus individually or as a complex.…”

Section: Fgf1 Targets Muc1-c To the Nucleusmentioning

confidence: 99%

MUC1 Oncoprotein Functions in Activation of Fibroblast Growth Factor Receptor Signaling

Ren

Raina²,

Chen³

et al. 2006

Molecular Cancer Research

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Activation of the fibroblast growth factor (FGF) receptor 3 (FGFR3) has been linked to the development of human cancers by mechanisms that are not well understood. The MUC1 oncoprotein is aberrantly overexpressed by certain hematologic malignancies and most human carcinomas. The present studies show that MUC1 associates with FGFR3. Stimulation of cells with FGF1 increased the interaction between MUC1 and FGFR3. FGF1 stimulation also induced c-Src-dependent tyrosine phosphorylation of the MUC1 cytoplasmic domain on a YEKV motif. FGF1-induced tyrosine phosphorylation of MUC1 was associated with increased binding of MUC1 to B-catenin and targeting of MUC1 and B-catenin to the nucleus. FGF1 also induced binding of MUC1 to the heat shock protein 90 (HSP90) chaperone by a mechanism dependent on phosphorylation of the YEKV motif. Notably, B-catenin and HSP90 compete for binding to the MUC1 cytoplasmic domain, indicating that MUC1 forms mutually exclusive complexes with these proteins. The results also show that inhibition of HSP90 with geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin attenuates FGF1-induced binding of MUC1 to HSP90 and targeting of MUC1 to the mitochondrial outer membrane. These findings indicate that FGF1 induces phosphorylation of MUC1 on YEKV and thereby activates two distinct pathways: (a) nuclear localization of MUC1 and B-catenin and (b) delivery of MUC1 to mitochondria by HSP90. (Mol Cancer Res 2006;4(11):873 -83)

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Section: Fgf1 Targets Muc1-c To the Nucleusmentioning

confidence: 99%

MUC1 Oncoprotein Functions in Activation of Fibroblast Growth Factor Receptor Signaling

Ren

Raina²,

Chen³

et al. 2006

Molecular Cancer Research

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“…This region forms a positively charged groove (Huber et al, 1997) and mediates heterotypic interactions, including binding to cadherins (Aberle et al, 1996;Barth et al, 1997), Axin/Axil (Behrens et al, 1998;Ikeda et al, 1998;Kikuchi, 1999a,b), APC (Rubinfeld et al, 1993;Su et al, 1993), Fascin (Tao et al, 1996), and SOXs (Zorn et al, 1999). Its structural similarity to the nuclear localization sequence receptors, the karyopherins/importins, presumably explains why bcatenin can enter the nucleus in a karyopherin/ importin-and RAN-independent manner (Fagotto et al, 1998;Yokoya et al, 1999). The carboxyl terminus of the ALPs has been identi®ed as a transactivation domain and is critical for Armadillo signaling Orsulic and Peifer, 1996;Simcha et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

A comparative evaluation of β-catenin and plakoglobin signaling activity

et al. 2000

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Vertebrates have two Armadillo-like proteins, b-catenin and plakoglobin. Mutant forms of b-catenin with oncogenic activity are found in many human tumors, but plakoglobin mutations are not commonly found. In fact, plakoglobin has been proposed to suppress tumorigenesis. To assess di erences between b-catenin and plakoglobin, we compared several of their biochemical properties. After transient transfection of 293T cells with an expression vector encoding either of the two proteins, soluble wild type b-catenin does not signi®-cantly accumulate, whereas soluble wild type plakoglobin is readily detected. As anticipated, b-catenin is stabilized by the oncogenic mutation S37A; however, the analogous mutation in plakoglobin (S28A) does not alter its halflife. S37A-b-catenin activates a TCF/LEF-dependent reporter 20-fold more potently than wild type b-catenin, and *5-fold more potently than wild type or S28A plakoglobin. These di erences may be attributable to an enhanced a nity of S37A b-catenin for LEF1 and TCF4, as observed here by immunoprecipitation assays. We show that the carboxyl-terminal domain is largely responsible for the di erence in signaling and that the Armadillo repeats account for the remainder of the di erence. The relatively weak signaling by plakoglobin and the failure of the S28A mutation to enhance its stability, may explain why plakoglobin mutations are infrequent in malignancies. Oncogene (2000) 19, 5720 ± 5728.

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“…APC, β-catenin, plakoglobin, plakophilins 1 and 2) are dual localization proteins that shuttle between the nucleus and the cytoplasm or plasma membrane (Chen et al, 2002;Fagotto et al, 1998;Korinek et al, 1997;Mertens et al, 2001;Morin et al, 1997;Neufeld et al, 2000;Rosin-Arbesfeld et al, 2000;Wiechens and Fagotto, 2001;Zhang et al, 2000). These observations are even more interesting in light of the fact that the major nuclear import receptor, importin-α, is composed almost entirely of Armadillo repeats (Conti et al, 1998;Gorlich, 1998).…”

mentioning

confidence: 99%

NLS-dependent nuclear localization of p120ctnis necessary to relieve Kaiso-mediated transcriptional repression

Kelly

Spring

Otchere

et al. 2004

Journal of Cell Science

104

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IntroductionThe Armadillo catenins, β-, γ-and p120 ctn , are multifunctional proteins whose malfunction contributes to tumor progression by various means (Behrens, 1999;Van Aken et al., 2001). They are members of a larger family of Armadillo proteins that are characterized by the presence of an Armadillo domain consisting of ten or more tandem copies of a 42 amino-acid Armadillo repeat (Peifer et al., 1994). The importance of the Armadillo catenins in tumorigenesis was first credited to their involvement in the multiprotein cadherin-catenin complex, which forms the major cell-cell adhesion system in epithelial cells. Dysfunction of this complex, through defects in any of its components, correlates with the metastatic phenotype iñ 50% of human carcinomas (Behrens, 1999;Yap, 1998). The key participant in this complex is the transmembrane glycoprotein and tumor suppressor E-cadherin that mediates cell-cell adhesion by the homophilic interactions of its extracellular domain. E-cadherin is then anchored to the underlying actin cytoskeleton by the classical catenin cofactors, β-and γ-catenin, that bind E-cadherin in a mutually exclusive manner (reviewed by Nollet et al., 1999). These classical catenins bind simultaneously to a highly conserved carboxy-terminal domain of E-cadherin and to the actinbinding protein α-catenin (reviewed by Behrens, 1999;Rimm et al., 1995). Like β-and γ-catenin, the nonclassical Armadillo catenin p120 ctn binds the cytoplasmic tail of E-cadherin via its Arm domain Reynolds et al., 1992). However, β-and γ-catenin compete for binding to the distal conserved catenin-binding domain, and function by anchoring E-cadherin to the actin cytoskeleton, whereas p120 ctn binds Ecadherin at a distinct juxtamembrane domain (JMD) and does not interact with α-catenin (Daniel and Reynolds, 1995;Thoreson et al., 2000). Importantly, the JMD is implicated in E-cadherin stability (Ireton et al., 2002;Pettitt et al., 2003), modulating cadherin adhesive strength (Aono et al., 1999;Ohkubo and Ozawa, 1999;Thoreson et al., 2000;Yap et al., 1998) and regulating cytoskeletal dynamics Grosheva et al., 2001;Noren et al., 2000), and as such p120 ctn is speculated to be a key mediator of these effects. This hypothesis is supported by recent observations that p120 ctn modulates the activities of RhoA, Rac and Cdc42, which are key mediators of cytoskeletal organization Grosheva et al., 2001;Noren et al., 2000).Originally identified as a Src kinase substrate (Reynolds et al., 1989), it was the structural similarity of p120 ctn to β-catenin that led to the discovery of p120 ctn as a novel catenin component of the cadherin complex (Daniel and Reynolds, 2675The Armadillo catenin p120 ctn regulates cadherin adhesive strength at the plasma membrane and interacts with the novel BTB/POZ transcriptional repressor Kaiso in the nucleus. The dual localization of p120 ctn at cell-cell junctions and in the nucleus suggests that its nucleocytoplasmic trafficking is tightly regulated. Here we report on the identification of a specific and h...

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Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of β-catenin

Cited by 400 publications

References 60 publications

MUC1 Oncoprotein Functions in Activation of Fibroblast Growth Factor Receptor Signaling

MUC1 Oncoprotein Functions in Activation of Fibroblast Growth Factor Receptor Signaling

A comparative evaluation of β-catenin and plakoglobin signaling activity

NLS-dependent nuclear localization of p120ctnis necessary to relieve Kaiso-mediated transcriptional repression

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