The tight junction protein ZO-2 has several functional nuclear export signals

González‐Mariscal, Lorenza; Ponce, Arturo; Alarcón, Lourdes; Jaramillo, Blanca Estela

doi:10.1016/j.yexcr.2006.07.006

Cited by 40 publications

(35 citation statements)

References 28 publications

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“…Figure 6B, a and b, shows how, as reported previously (Gonzalez-Mariscal et al, 2006), the microinjected WT amino-ZO-2-GST protein exits the nucleus in a LMB-sensitive way. Now, we show that the microinjected amino-ZO-2-GST Figure 3.…”

Section: Novel Protein Kinase C Regulates the Exit Of Zo-2 From The Nsupporting

confidence: 77%

“…The amino-ZO-2-GST construct described previously by us (Gonzalez-Mariscal et al, 2006) as well as its derived mutant S369A were used to transform competent Escherichia coli (catalog no. 230196, Artic Express RP competent cells; Stratagene, La Jolla, CA).…”

Section: Zo-2 Fusion Proteinsmentioning

confidence: 99%

“…Previously, through a nuclear microinjection assay, we had shown that ZO-2 NES-1 could not export the reporter protein ovalbumin (Jaramillo et al, 2004), unless a phosphomimetic mutation was performed on the putative PKC phosphorylation site, located at Ser369 (Gonzalez-Mariscal et al, 2006). This observation prompted us to analyze the impact of Ser369 phosphorylation on the nuclear export of fulllength ZO-2.…”

Section: Recruitment Of Zo-2 To the Nucleus Is High After Transfectiomentioning

confidence: 99%

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Phosphorylation of Zona Occludens-2 by Protein Kinase Cε Regulates Its Nuclear Exportation

Chamorro

Alarcón

Ponce

et al. 2009

MBoC

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Here, we have analyzed the subcellular destiny of newly synthesized tight junction protein zona occludens (ZO)-2. After transfection in sparse cells, 74% of cells exhibit ZO-2 at the nucleus, and after 18 h the value decreases to 17%. The mutation S369A located within the nuclear exportation signal 1 of ZO-2 impairs the nuclear export of the protein. Because Ser369 represents a putative protein kinase C (PKC) phosphorylation site, we tested the effect of PKC inhibition and stimulation on the nuclear export of ZO-2. Our results strongly suggest that the departure of ZO-2 from the nucleus is regulated by phosphorylation at Ser369 by novel PKC. To test the route taken by ZO-2 from synthesis to the plasma membrane, we devised a novel nuclear microinjection assay in which the nucleus served as a reservoir for anti-ZO-2 antibody. Through this assay, we demonstrate that a significant amount of newly synthesized ZO-2 goes into the nucleus and is later relocated to the plasma membrane. These results constitute novel information for understanding the mechanisms that regulate the intracellular fate of ZO-2.

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Section: Novel Protein Kinase C Regulates the Exit Of Zo-2 From The Nsupporting

confidence: 77%

Section: Zo-2 Fusion Proteinsmentioning

confidence: 99%

Section: Recruitment Of Zo-2 To the Nucleus Is High After Transfectiomentioning

confidence: 99%

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Phosphorylation of Zona Occludens-2 by Protein Kinase Cε Regulates Its Nuclear Exportation

Chamorro

Alarcón

Ponce

et al. 2009

MBoC

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“…Thus, in the nucleus, ZO-2 has been described to colocalize with splicing factor SC-35, with scaffold attachment factor-B (SAF-B), and with transcription factors Jun and Fos, and CCAAT/enhancer-binding protein (C/EBP) [1,3,4]. The ability of ZO-2 to shuttle from the membrane to the cytosol or nucleus relies on the presence of nuclear exporting (NES) and nuclear localization (NLS) signals on its sequence [1,2,5]. However, the functional consequences of ZO-2 differential subcellular localization are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells

Luczka

Syne

Nawrocki‐Raby

et al. 2013

Clin Exp Metastasis

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During tumor invasion, tumor epithelial cells acquire migratory and invasive properties involving important phenotypic alterations. Among these changes, one can observe reorganization or a loss of cell-cell adhesion complexes such as tight junctions (TJs). TJs are composed of transmembrane proteins (occludin, claudins) linked to the actin cytoskeleton through cytoplasmic adaptor molecules including those of the zonula occludens family (ZO-1, -2, -3). We here evaluated the potential role of ZO-2 in the acquisition of invasive properties by tumor cells. In vivo, we showed a decrease of ZO-2 expression in bronchopulmonary cancers, with a preferential localization in the cytoplasm. In addition, in vitro, the localization of ZO-2 varied according to invasive properties of tumor cells, with a cytoplasmic localization correlating with invasion. In addition, we demonstrated that ZO-2 inhibition increases invasive and migrative capacities of invasive tumor cells. This was associated with an increase of MT1-MMP. These results suggest that ZO-2, besides its structural role in tight junction assembly, can act also as a repressor of tumor progression through its ability to reduce the expression of tumor-promoting genes in invasive tumor cells.

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“…Thus, in confluent monolayers ZO-2 is concentrated at the TJ, whereas in sparse cultures it is enriched at the nucleus and cell-cell contacts. Shuttling between the nucleus and the plasma membrane is possible due to the presence of several functional nuclear localization and exportation signals in the sequence of the protein (Jaramillo et al, 2004;Gonzalez-Mariscal et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Cyclin D1 Is Transcriptionally Down-Regulated by ZO-2 via an E Box and the Transcription Factor c-Myc

Huerta¹,

Muñoz²,

Tapia

et al. 2007

MBoC

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Recent reports have indicated the participation of tight junction (TJ) proteins in the regulation of gene expression and cell proliferation. Here, we have studied the role of zona occludens (ZO)-2, a TJ peripheral protein, in the regulation of cyclin D1 transcription. We found that ZO-2 down-regulates cyclin D1 transcription in a dose-dependent manner. To understand how ZO-2 represses cyclin D1 promoter activity, we used deletion analyses and found that ZO-2 negatively regulates cyclin D1 transcription via an E box and that it diminishes cell proliferation. Because ZO-2 does not associate directly with DNA, electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay were used to identify the transcription factors mediating the ZO-2-repressive effect. c-Myc was found to bind the E box present in the cyclin D1 promoter, and the overexpression of c-Myc augmented the inhibition generated by ZO-2 transfection. The presence of ZO-2 and c-Myc in the same complex was further demonstrated by immunoprecipitation. ChIP and reporter gene assays using histone deacetylases (HDACs) inhibitors demonstrated that HDACs are necessary for ZO-2 repression and that HDAC1 is recruited to the E box. We conclude that ZO-2 down-regulates cyclin D1 transcription by interacting with the c-Myc/E box element and by recruiting HDAC1.

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The tight junction protein ZO-2 has several functional nuclear export signals

Cited by 40 publications

References 28 publications

Phosphorylation of Zona Occludens-2 by Protein Kinase Cε Regulates Its Nuclear Exportation

Phosphorylation of Zona Occludens-2 by Protein Kinase Cε Regulates Its Nuclear Exportation

Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells

Cyclin D1 Is Transcriptionally Down-Regulated by ZO-2 via an E Box and the Transcription Factor c-Myc

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